In
cell biologyCell biology is an academic discipline that studies cells – their physiological properties, their structure, the organelles they contain, interactions with their environment, their life cycle, division and death. This is done both on a microscopic and molecular level...
, the
nucleus (pl.
nuclei; from
LatinLatin is an Italic language originally spoken in Latium and Ancient Rome. Through the Roman conquest, Latin spread throughout the Mediterranean and a large part of Europe...
or , meaning kernel), also sometimes referred to as the "control center", is a membrane-enclosed
organelleIn cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid membrane....
found in
eukaryoticA eukaryote is an organism whose cells contain complex structures enclosed within membranes. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear envelope, within which the genetic material is carried...
cellsThe cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of an organism that is classified as living, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos...
. It contains most of the cell's
genetic materialGenetics, , a discipline of biology, is the science of heredity and variation in living organisms. The fact that living things inherit traits from their parents has been used since prehistoric times to improve crop plants and animals through selective breeding...
, organized as multiple long linear
DNADeoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms and some viruses. The main role of DNA molecules is the long-term storage of information...
molecules in complex with a large variety of
proteinProteins are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer chain are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues...
s, such as
histoneIn biology, histones are strongly alkaline proteins found in eukaryotic cell nuclei, which package and order the DNA into structual units called nucleosomes. They are the chief protein components of chromatin, act as spools around which DNA winds, and play a role in gene regulation. Without...
s, to form
chromosomeA chromosome is an organized structure of DNA and protein that is found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions...
s. The
geneA gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cells and pass genetic traits to offspring...
s within these chromosomes are the cell's
nuclear genomeIn modern molecular biology the genome refers to all of its hereditary information encoded in DNA .The genome includes both the genes and the non-coding sequences of the DNA. The term was adapted in 1920 by Hans Winkler, Professor of Botany at the University of Hamburg, Germany...
. The function of the nucleus is to maintain the integrity of these genes and to control the activities of the cell by regulating
gene expressionGene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as rRNA genes or tRNA genes, the product is a functional RNA...
--the nucleus is therefore the control center of the cell.
The main structures making up the nucleus are the
nuclear envelopeThe nuclear envelope is a double lipid bilayer that encloses the genetic material in eukaryotic cells. The nuclear envelope also serves as the physical barrier, separating the contents of the nucleus from the cytosol...
, a double membrane that encloses the entire organelle and separates its contents from the cellular
cytoplasmThe cytoplasm is the part of a cell that is enclosed within the cell membrane. In eukaryotic cells, the cytoplasm contains organelles, such as mitochondria, which are filled with liquid that is kept separate from the rest of the cytoplasm by biological membranes. The contents of the cell nucleus...
, and the
nuclear laminaThe nuclear lamina is a dense fibrillar network inside the nucleus of an eukaryotic cell. It is composed of intermediate filaments and membrane associated proteins. Besides providing mechanical support, the nuclear lamina regulates important cellular events such as DNA replication and cell division...
, a meshwork within the nucleus that adds mechanical support, much like the
cytoskeletonThe cytoskeleton is a cellular "scaffolding" or "skeleton" contained within the cytoplasm. The cytoskeleton is present in all cells; it was once thought this structure was unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
supports the cell as a whole. Because the nuclear membrane is impermeable to most molecules,
nuclear poreNuclear pores are large protein complexes that cross the nuclear envelope, which is the double membrane surrounding the eukaryotic cell nucleus. There are about on average 2000 nuclear pore complexes in the nuclear envelope of a vertebrate cell, but it varies depending on cell type and the stage in...
s are required to allow movement of molecules across the envelope. These pores cross both of the membranes, providing a channel that allows free movement of small molecules and
ionAn ion is an atom or molecule where the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge...
s. The movement of larger molecules such as proteins is carefully controlled, and requires active transport regulated by carrier proteins.
Nuclear transportThe entry and exit of large molecules from the cell nucleus is tightly controlled by the nuclear pore complexes . Although small molecules can enter the nucleus without regulation, macromolecules such as RNA and proteins require association with karyopherins called importins to enter the nucleus...
is crucial to cell function, as movement through the pores is required for both gene expression and chromosomal maintenance.
Although the interior of the nucleus does not contain any membrane-bound subcompartments, its contents are not uniform, and a number of
subnuclear bodies exist, made up of unique proteins,
RNARibonucleic acid is a biologically important type of molecule that consists of a long chain of nucleotide units. Each nucleotide consists of a nitrogenous base, a ribose sugar, and a phosphate...
molecules, and particular parts of the chromosomes. The best known of these is the
nucleolusThe nucleolus is a non-membrane bound structure composed of proteins and nucleic acids found within the nucleus. Ribosomal RNA is transcribed and assembled within the nucleolus...
, which is mainly involved in the assembly of
ribosomeRibosomes are complexes of RNA and protein that are found in all cells. The ribosome is part of the mechanism that translates the DNA sequence into the protein sequence. Ribosomes from bacteria, archaea and eukaryotes , have significantly different structure and RNA...
s. After being produced in the nucleolus, ribosomes are exported to the cytoplasm where they translate mRNA.
History
The nucleus was the first organelle to be discovered. The probably oldest preserved drawing dates back to the early microscopist Antonie van Leeuwenhoek (1632 – 1723). He observed a "Lumen", the nucleus, in the
red blood cellRed blood cells are the most common type of blood cell and the vertebrate body's principal means of delivering oxygen to the body tissues via the blood. They take up oxygen in the lungs or gills and release it while squeezing through the body's capillaries. The cells are filled with hemoglobin, a...
s of
salmonSalmon is the common name for several species of fish of the family Salmonidae. Several other fish in the family are called trout; the difference is often attributed to the migratory life of the salmon as compared to the residential behaviour of trout, a distinction that holds true for the Salmo...
. Unlike mammalian red blood cells, those of other vertebrates still possess nuclei.
The nucleus was also described by
Franz BauerFranz Andreas Bauer was an Austrian microscopist and botanical artist.Born in Feldsberg Franz Andreas Bauer (later Francis) (March 14, 1758 – December 11, 1840) was an Austrian microscopist and botanical artist.Born in Feldsberg Franz Andreas Bauer (later Francis) (March 14, 1758 – December 11,...
in 1804 and in more detail in 1831 by Scottish botanist
Robert BrownRobert Brown FRS was a Scottish botanist who made important contributions to botany largely through his pioneering use of the microscope...
in a talk at the
Linnean Society of LondonThe Linnean Society of London is the world's premier society for the study and dissemination of taxonomy and natural history. It publishes a Zoological Journal, as well as Botanical and Biological Journals...
. Brown was studying orchids microscopically when he observed an opaque area, which he called the areola or nucleus, in the cells of the flower's outer layer.
He did not suggest a potential function. In 1838 Matthias Schleiden proposed that the nucleus plays a role in generating cells, thus he introduced the name "Cytoblast" (cell builder). He believed that he had observed new cells assembling around "cytoblasts".
Franz MeyenFranz Julius Ferdinand Meyen was a German physician and botanist.Meyen was born in Tilsit. In 1830 he wrote Phytotomie, the first review of plant anatomy...
was a strong opponent of this view having already described cells multiplying by division and believing that many cells would have no nuclei. The idea that cells can be generated de novo, by the "cytoblast" or otherwise, contradicted work by
Robert RemakRobert Remak was a Polish/German embryologist, physiologist, and neurologist, born in Posen, Prussia. Dr. Remak obtained his medical degree from Friedrich Wilhelm University in Berlin in 1838 specializing in neurology. He is best known for reducing Karl Ernst von Baer's four germ layers to three:...
(1852) and
Rudolf VirchowRudolf Ludwig Karl Virchow was a German doctor, anthropologist, public health activist, pathologist, prehistorian, biologist and politician...
(1855) who decisively propagated the new paradigm that cells are generated solely by cells ("Omnis cellula e cellula"). The function of the nucleus remained unclear.
Between 1876 and 1878 Oscar Hertwig published several studies on the fertilization of
sea urchinSea urchins or urchins are small, spiny, globular animals that compose part of class Echinoidea. They are found in oceans all over the world. Their shell, or "test", is round and spiny, typically from 3 to 10 cm across. Common colors include black and dull shades of green, olive, brown, purple,...
eggs, showing that the nucleus of the
spermThe term sperm is derived from the Greek word sperma and refers to the male reproductive cells. In the types of sexual reproduction known as anisogamy and oogamy, there is a marked difference in the size of the gametes with the smaller one being termed the "male" or sperm cell...
enters the
oocyteAn oocyte, ovocyte, or rarely ocyte, is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is part of the ovary development. The germ cells produce a primordial germ cell which becomes an oogonium which marks the start of mitosis...
and fuses with its nucleus. This was the first time it was suggested that an individual develops from a (single) nucleated cell. This was in contradiction to
Ernst HaeckelErnst Heinrich Philipp August Haeckel ,also written von Haeckel, was an eminent German biologist, naturalist, philosopher, physician, professor and artist who discovered, described and named thousands of new species, mapped a genealogical tree relating all life forms, and coined many terms in...
's theory that the complete phylogeny of a species would be repeated during embryonic development, including generation of the first nucleated cell from a "Monerula", a structureless mass of primordial mucus ("Urschleim"). Therefore, the necessity of the sperm nucleus for fertilization was discussed for quite some time. However, Hertwig confirmed his observation in other animal groups, e.g. amphibians and molluscs.
Eduard StrasburgerEduard Adolf Strasburger was a Polish-German professor who was one of the most famous botanists of the 19th century.He was born in Warsaw, Poland, son of Edward Bogumil Strasburger...
produced the same results for plants (1884). This paved the way to assign the nucleus an important role in heredity. In 1873
August WeismannFriedrich Leopold August Weismann was a German evolutionary biologist. Ernst Mayr ranked him the second most notable evolutionary theorist of the 19th century, after Charles Darwin....
postulated the equivalence of the maternal and paternal germ
cells for heredity. The function of the nucleus as carrier of genetic information became clear only later, after
mitosisMitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets in two daughter nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two daughter cells containing...
was discovered and the
Mendelian rulesMendelian inheritance is a set of primary tenets relating to the transmission of hereditary characteristics from parent organisms to their children; it underlies much of genetics. They were initially derived from the work of Gregor Mendel published in 1865 and 1866 which was "re-discovered" in...
were rediscovered at the beginning of the 20th century; the chromosome theory of heredity was developed.
Structures
The nucleus is the largest cellular
organelleIn cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid membrane....
in animals.
In
mammalMammals are a class of vertebrate animals whose females are characterized by the possession of mammary glands while both males and females are characterized by sweat glands, hair, three middle ear bones used in hearing, and a neocortex region in the brain.Mammals are divided into three main...
ian cells, the average diameter of the nucleus is approximately 6 micrometers (μm), which occupies about 10% of the total cell volume. The viscous liquid within it is called
nucleoplasmSimilar to the cytoplasm of a cell, the nucleus contains nucleoplasm or nuclear sap. The nucleoplasm is one of the types of protoplasm, and it is enveloped by the nuclear membrane or nuclear envelope. The nucleoplasm is a highly viscous liquid that surrounds the chromosomes and nucleoli...
, and is similar in composition to the
cytosolThe cytosol or intracellular fluid is the liquid found inside cells. In eukaryotes this liquid is separated by cell membranes from the contents of the organelles suspended in the cytosol, such as the mitochondrial matrix inside the mitochondrion...
found outside the nucleus. It appears as a dense, roughly spherical organelle.
Nuclear envelope and pores
The
nuclear envelopeThe nuclear envelope is a double lipid bilayer that encloses the genetic material in eukaryotic cells. The nuclear envelope also serves as the physical barrier, separating the contents of the nucleus from the cytosol...
otherwise known as nuclear membrane consists of two
cellular membranesThe cell membrane is the biological membrane separating the interior of a cell from the outside environment....
, an inner and an outer membrane, arranged parallel to one another and separated by 10 to 50 nanometers (nm). The nuclear envelope completely encloses the nucleus and separates the cell's genetic material from the surrounding cytoplasm, serving as a barrier to prevent
macromoleculeA macromolecule is a very large molecule most often created by some form of polymerization. In the context of biochemistry, the term may be applied to the four conventional biopolymers , as well as non-polymeric molecules with large molecular mass such as macrocycles...
s from diffusing freely between the nucleoplasm and the cytoplasm. The outer nuclear membrane is continuous with the membrane of the rough endoplasmic reticulum (RER), and is similarly studded with ribosomes. The space between the membranes is called the perinuclear space and is continuous with the RER
lumenA lumen in biology is the inside space of a tubular structure, such as an artery or intestine...
.
Nuclear pores, which provide aqueous channels through the envelope, are composed of multiple proteins, collectively referred to as nucleoporins. The pores are about 125 million
daltonsThe unified atomic mass unit or atomic mass unit , or dalton or, sometimes, universal mass unit , is a unit of mass used to express atomic and molecular masses...
in molecular weight and consist of around 50 (in
yeastYeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with about 1,500 species currently described; they dominate fungal diversity in the oceans. Most reproduce asexually by budding, although a few do so by binary fission...
) to 100 proteins (in
vertebrateVertebrates are members of the subphylum Vertebrata, chordates with backbones or spinal columns. About 58,000 species of vertebrates have been described. Vertebrata is the largest subphylum of chordates, and contains many familiar groups of large land animals. Vertebrates comprise cyclostomes, bony...
s). The pores are 100 nm in total diameter; however, the gap through which molecules freely diffuse is only about 9 nm wide, due to the presence of regulatory systems within the center of the pore. This size allows the free passage of small water-soluble molecules while preventing larger molecules, such as
nucleic acidA nucleic acid is a macromolecule composed of chains of monomeric nucleotides. In biochemistry these molecules carry genetic information or form structures within cells. The most common nucleic acids are deoxyribonucleic acid and ribonucleic acid . Nucleic acids are universal in living things, as...
s and larger proteins, from inappropriately entering or exiting the nucleus. These large molecules must be actively transported into the nucleus instead. The nucleus of a typical mammalian cell will have about 3000 to 4000 pores throughout its envelope, each of which contains a donut-shaped, eightfold-symmetric ring-shaped structure at a position where the inner and outer membranes fuse. Attached to the ring is a structure called the
nuclear basket that extends into the nucleoplasm, and a series of filamentous extensions that reach into the cytoplasm. Both structures serve to mediate binding to nuclear transport proteins.
Most proteins, ribosomal subunits, and some RNAs are transported through the pore complexes in a process mediated by a family of transport factors known as
karyopherinKaryopherins are a group of proteins involved in transporting molecules through the pores of the nuclear envelope ....
s. Those karyopherins that mediate movement into the nucleus are also called importins, while those that mediate movement out of the nucleus are called exportins. Most karyopherins interact directly with their cargo, although some use adaptor proteins.
Steroid hormoneSteroid hormones are steroids that act as hormones. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestagens...
s such as
cortisolCortisol is a corticosteroid hormone or glucocorticoid produced by the adrenal cortex, that is part of the adrenal gland . It is usually referred to as the "stress hormone" as it is involved in response to stress and anxiety, controlled by CRH...
and
aldosteroneAldosterone is a hormone that increases the reabsorption of sodium and water and the release of potassium in the kidneys. This increases blood volume and, therefore, increases blood pressure. Many drugs, such as spironolactone, lower blood pressure by blocking the aldosterone receptor...
, as well as other small lipid-soluble molecules involved in intercellular
signalingCell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...
can diffuse through the cell membrane and into the cytoplasm, where they bind
nuclear receptorIn the field of molecular biology, nuclear receptors are a class of proteins found within the interior of cells that are responsible for sensing the presence of steroid and thyroid hormones and certain other molecules...
proteins that are trafficked into the nucleus. There they serve as
transcription factorIn the field of molecular biology, a transcription factor is a protein that binds to specific DNA sequences and thereby controls the transfer of genetic information from DNA to mRNA...
s when bound to their
ligandIn biochemistry and pharmacology, a ligand is a substance that is able to bind to and form a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as...
; in the absence of ligand many such receptors function as
histone deacetylaseHistone deacetylases are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. Its action is opposite to that of histone acetyltransferase.-Subtypes:...
s that repress gene expression.
Nuclear lamina
In animal cells, two networks of intermediate filaments provide the nucleus with mechanical support: the
nuclear laminaThe nuclear lamina is a dense fibrillar network inside the nucleus of an eukaryotic cell. It is composed of intermediate filaments and membrane associated proteins. Besides providing mechanical support, the nuclear lamina regulates important cellular events such as DNA replication and cell division...
forms an organized meshwork on the internal face of the envelope, while less organized support is provided on the cytosolic face of the envelope. Both systems provide structural support for the nuclear envelope and anchoring sites for chromosomes and nuclear pores.
The nuclear lamina is mostly composed of
laminNuclear Lamins, also known as Class V intermediate filaments, are fibrous proteins providing structural function and transcriptional regulation in the cell nucleus. Nuclear lamins interact with membrane-associated proteins to form the nuclear lamina on the interior of the nuclear envelope...
proteins. Like all proteins, lamins are synthesized in the cytoplasm and later transported into the nucleus interior, where they are assembled before being incorporated into the existing network of nuclear lamina. Lamins are also found inside the nucleoplasm where they form another regular structure, known as the
nucleoplasmic veil, that is visible using fluorescence microscopy. The actual function of the veil is not clear, although it is excluded from the
nucleolusThe nucleolus is a non-membrane bound structure composed of proteins and nucleic acids found within the nucleus. Ribosomal RNA is transcribed and assembled within the nucleolus...
and is present during
interphaseInterphase is the phase of the cell cycle in which the cell spends the majority of its time and performs the majority of its purposes including preparation for cell division. In preparation for cell division it increases its size and number of organelles, and makes a copy of its DNA...
. The lamin structures that make up the veil bind
chromatinChromatin is the complex combination of DNA and protein that makes up chromosomes. It is found inside the nuclei of eukaryotic cells. It is divided between heterochromatin and euchromatin forms....
and disrupting their structure inhibits transcription of protein-coding genes.
Like the components of other
intermediate filamentIntermediate filaments are a family of related proteins that share common structural and sequence features. Intermediate filaments have an average diameter of 10 nanometers, which is between that of actin and microtubules, although they were initially designated 'intermediate' because their...
s, the lamin
monomerA monomer is a small molecule that may become chemically bonded to other monomers to form a polymer...
contains an alpha-helical domain used by two monomers to coil around each other, forming a
dimerA dimer is a chemical or biological entity consisting of two structurally similar subunits called monomers, which are joined by bonds, which can be strong or weak.- Organic chemistry :...
structure called a
coiled coilA coiled coil is a structural motif in proteins, in which 2-7 alpha-helices are coiled together like the strands of a rope . Many coiled coil type proteins are involved in important biological functions such as the regulation of gene expression e.g. transcription factors...
. Two of these dimer structures then join side by side, in an
antiparallelIn biochemistry, two molecules are antiparallel if they run side-by-side in opposite directions.In DNA, the 5' carbon is located at the top of the leading strand, and the 3' carbon is located at the lower section of the lagging strand. The nucleotides are similar and parallel, but they go in...
arrangement, to form a tetramer called a
protofilament. Eight of these protofilaments form a lateral arrangement that is twisted to form a ropelike
filament. These filaments can be assembled or disassembled in a dynamic manner, meaning that changes in the length of the filament depend on the competing rates of filament addition and removal.
Mutations in lamin genes leading to defects in filament assembly are known as
laminopathies. The most notable laminopathy is the family of diseases known as
progeriaProgeria is an extremely rare, severe, genetic condition wherein symptoms resembling aspects of aging are manifested at an early age. Approximately one in four-million people are diagnosed with this condition...
, which causes the appearance of premature aging in its sufferers. The exact mechanism by which the associated biochemical changes give rise to the aged
phenotypeA phenotype is any observable characteristic or trait of an organism: such as its morphology, development, biochemical or physiological properties, or behavior. Phenotypes result from the expression of an organism's genes as well as the influence of environmental factors and possible interactions...
is not well understood.
Chromosomes
The cell nucleus contains the majority of the cell's genetic material, in the form of multiple linear
DNADeoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms and some viruses. The main role of DNA molecules is the long-term storage of information...
molecules organized into structures called
chromosomeA chromosome is an organized structure of DNA and protein that is found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions...
s. During most of the
cell cycleThe cell cycle, or cell-division cycle, is the series of events that take place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
these are organized in a DNA-protein complex known as
chromatinChromatin is the complex combination of DNA and protein that makes up chromosomes. It is found inside the nuclei of eukaryotic cells. It is divided between heterochromatin and euchromatin forms....
, and during cell division the chromatin can be seen to form the well defined
chromosomeA chromosome is an organized structure of DNA and protein that is found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions...
s familiar from a
karyotypeA karyotype is the charcteristic chromosome complement of a eukaryote species. The term may also be used of a cell, or an individual. The preparation and study of karyotypes is part of cytogenetics....
. A small fraction of the cell's genes are located instead in the mitochondria.
There are two types of chromatin.
EuchromatinEuchromatin is a lightly packed form of chromatin that is rich in gene concentration, and is often under active transcription. Unlike heterochromatin, it is found in both cells with nuclei and cells without nuclei...
is the less compact DNA form, and contains genes that are frequently
expressedGene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as rRNA genes or tRNA genes, the product is a functional RNA...
by the cell. The other type,
heterochromatinHeterochromatin is a tightly packed form of DNA. Its major characteristic is that transcription is limited. As such, it is a means to control gene expression, through regulation of the transcription initiation.-Structure:...
, is the more compact form, and contains DNA that are infrequently transcribed. This structure is further categorized into
facultative heterochromatin, consisting of genes that are organized as heterochromatin only in certain cell types or at certain stages of development, and
constitutive heterochromatin that consists of chromosome structural components such as
telomereA telomere is a region of repetitive DNA at the end of a chromosome, which protects the end of the chromosome from destruction. Its name is derived from the Greek nouns telos "end" and merοs "part"....
s and
centromereA centromere is a region of DNA typically found near the middle of a chromosome where two identical sister chromatids come in contact. It is involved in cell division as the point of mitotic spindle.-Function:...
s. During interphase the chromatin organizes itself into discrete individual patches, called
chromosome territories. Active genes, which are generally found in the euchromatic region of the chromosome, tend to be located towards the chromosome's territory boundary.
Antibodies to certain types of chromatin organization, particularly
nucleosomeNucleosomes form the fundamental repeating units of eukaryotic chromatin, which is used to pack the large eukaryotic genomes into the nucleus while still ensuring appropriate access to it...
s, have been associated with a number of
autoimmune diseaseAutoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. This may be restricted to certain organs or involve a particular tissue in different places Autoimmune...
s, such as
systemic lupus erythematosusSystemic lupus erythematosus is a chronic autoimmune connective tissue disease that can affect any part of the body...
. These are known as
anti-nuclear antibodiesAnti-nuclear antibodies are antibodies directed against contents of the cell nucleus....
(ANA) and have also been observed in concert with
multiple sclerosisMultiple sclerosis is an idiopathic disease of suspected autoimmune cause, in which the body's immune response attacks a person's central nervous system , leading to demyelination. Disease onset usually occurs in young adults, and it is more common in females...
as part of general immune system dysfunction. As in the case of progeria, the role played by the antibodies in inducing the symptoms of autoimmune diseases is not obvious.
Nucleolus
The
nucleolusThe nucleolus is a non-membrane bound structure composed of proteins and nucleic acids found within the nucleus. Ribosomal RNA is transcribed and assembled within the nucleolus...
is a discrete densely stained structure found in the nucleus. It is not surrounded by a membrane, and is sometimes called a
suborganelle. It forms around
tandemTandem is a Latin adverb meaning "at length" or "finally." In English, the term was originally used for two or more draft horses harnessed one behind another as opposed to side-by-side...
repeats of rDNA, DNA coding for
ribosomal RNARibosomal RNA is the central component of the ribosome, the protein manufacturing machinery of all living cells. The function of the rRNA is to provide a mechanism for decoding mRNA into amino acids and to interact with the tRNAs during translation by providing peptidyl transferase activity.The...
(rRNA). These regions are called nucleolar organizer regions (NOR). The main roles of the nucleolus are to synthesize rRNA and assemble ribosomes. The structural cohesion of the nucleolus depends on its activity, as ribosomal assembly in the nucleolus results in the transient association of nucleolar components, facilitating further ribosomal assembly, and hence further association. This model is supported by observations that inactivation of rDNA results in intermingling of nucleolar structures.
The first step in ribosomal assembly is transcription of the rDNA, by a protein called
RNA polymerase IRNA polymerase I is, in eukaryotes, the only enzyme that transcribes ribosomal RNA a type of RNA which accounts for over 50% of the total RNA synthesized in a cell....
, forming a large pre-rRNA precursor. This is cleaved into the subunits 5.8S, 18S, and 28S rRNA. The transcription, post-transcriptional processing, and assembly of rRNA occurs in the nucleolus, aided by small nucleolar RNA (snoRNA) molecules, some of which are derived from spliced
intronAn intron is a DNA region within a gene that is not translated into protein. These non-coding sections are transcribed to precursor mRNA and some other RNAs , and subsequently removed by a process called splicing during the processing to mature RNA. After intron splicing An intron is a DNA region...
s from
messenger RNAMessenger ribonucleic acid is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino...
s encoding genes related to ribosomal function. The assembled ribosomal subunits are the largest structures passed through the nuclear pores.
When observed under the
electron microscopeAn electron microscope is a type of microscope, a scientific instrument which is used to magnify things on a fine scale. That uses a particle beam of electrons to illuminate a specimen and create a highly-magnified image...
, the nucleolus can be seen to consist of three distinguishable regions: the innermost
fibrillar centers (FCs), surrounded by the
dense fibrillar component (DFC), which in turn is bordered by the
granular component (GC). Transcription of the rDNA occurs either in the FC or at the FC-DFC boundary, and therefore when rDNA transcription in the cell is increased more FCs are detected. Most of the cleavage and modification of rRNAs occurs in the DFC, while the latter steps involving protein assembly onto the ribosomal subunits occurs in the GC.
Other subnuclear bodies
Subnuclear structure sizes
| Structure name |
Structure diameter |
| Cajal bodies |
0.2–2.0 µm |
| PIKA |
5 µm |
| PML bodies |
0.2–1.0 µm |
| Paraspeckles |
0.2–1.0 µm |
| Speckles |
20–25 nm |
Besides the nucleolus, the nucleus contains a number of other non-membrane delineated bodies. These include Cajal bodies, Gemini of coiled bodies, polymorphic interphase karyosomal association (PIKA), promyelocytic leukaemia (PML) bodies,
paraspeckleParaspeckles in anatomy are irregularly shaped sub-cellular compartments, approximately 0.2-1 μm in size, found in the nucleus' interchromatin space . First documented in HeLa cells, where there are generally 10-30 per nucleus, paraspeckles are now known to also exist in all human primary cells,...
s and splicing speckles. Although little is known about a number of these domains, they are significant in that they show that the nucleoplasm is not uniform mixture, but rather contains organized functional subdomains.
Other subnuclear structures appear as part of abnormal disease processes. For example, the presence of small intranuclear rods have been reported in some cases of
nemaline myopathyNemaline myopathy is a congenital, hereditary neuromuscular disorder that causes muscle weakness, generally nonprogressive, of varying severity....
. This condition typically results from mutations in
actinActin is a globular, roughly 42-kDa protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
, and the rods themselves consist of mutant actin as well as other cytoskeletal proteins.
Cajal bodies and gems
A nucleus typically contains between 1 and 10 compact structures called
Cajal bodiesCajal bodies are spherical sub-organelles found in the nucleus of proliferative cells like tumor cells, or metabolically active cells like neurons...
or coiled bodies (CB), whose diameter measures between 0.2 µm and 2.0 µm depending on the cell type and species. When seen under an
electron microscopeAn electron microscope is a type of microscope, a scientific instrument which is used to magnify things on a fine scale. That uses a particle beam of electrons to illuminate a specimen and create a highly-magnified image...
, they resemble balls of tangled thread and are dense foci of distribution for the protein
coilinCoilin is a protein that in humans is encoded by the COIL gene.Coilin protein is one of the main molecular components of Cajal bodies . Cajal bodies are nuclear suborganelles of varying number and composition that are involved in the post-transcriptional modification of small nuclear and small...
. CBs are involved in a number of different roles relating to RNA processing, specifically
small nucleolar RNASmall nucleolar RNAs are a class of small RNA molecules that guide chemical modifications of other RNAs, mainly ribosomal RNAs, transfer RNAs and small nuclear RNAs...
(snoRNA) and
small nuclear RNASmall nuclear RNA is a class of small RNA molecules that are found within the nucleus of eukaryotic cells. They are transcribed by RNA polymerase II or RNA polymerase III and are involved in a variety of important processes such as RNA splicing , regulation of transcription factors or RNA...
(snRNA) maturation, and histone mRNA modification.
Similar to Cajal bodies are Gemini of coiled bodies, or gems, whose name is derived from the
Gemini constellationGemini is one of the constellations of the zodiac. Its name is Latin for "twins", and it is associated with the twins Castor and Pollux in Greek mythology. Its symbol is . It lies between Taurus to the west and the dim Cancer to the east, with Auriga and Lynx to the north and Monoceros and Canis...
in reference to their close "twin" relationship with CBs. Gems are similar in size and shape to CBs, and in fact are virtually indistinguishable under the microscope. Unlike CBs, gems do not contain
small nuclear ribonucleoproteinssnRNPs , or small nuclear ribonucleoproteins, are particles that combine with pre-mRNA and various proteins to form spliceosomes . SnRNPs "recognize" the places along a strand of pre-mRNA and are essential in the removal of introns...
(snRNPs), but do contain a protein called
survivor of motor neurons (SMN) whose function relates to snRNP biogenesis. Gems are believed to assist CBs in snRNP biogenesis, though it has also been suggested from microscopy evidence that CBs and gems are different manifestations of the same structure.
PIKA and PTF domains
PIKA domains, or polymorphic interphase karyosomal associations, were first described in microscopy studies in 1991. Their function was and remains unclear, though they were not thought to be associated with active DNA replication, transcription, or RNA processing. They have been found to often associate with discrete domains defined by dense localization of the
transcription factorIn the field of molecular biology, a transcription factor is a protein that binds to specific DNA sequences and thereby controls the transfer of genetic information from DNA to mRNA...
PTF, which promotes transcription of snRNA.
PML bodies
Promyelocytic leukaemia bodies (PML bodies) are spherical bodies found scattered throughout the nucleoplasm, measuring around 0.2–1.0 µm. They are known by a number of other names, including nuclear domain 10 (ND10), Kremer bodies, and PML oncogenic domains. They are often seen in the nucleus in association with Cajal bodies and cleavage bodies. It has been suggested that they play a role in regulating transcription.
Paraspeckles
Discovered by Fox et al. in 2002,
paraspeckleParaspeckles in anatomy are irregularly shaped sub-cellular compartments, approximately 0.2-1 μm in size, found in the nucleus' interchromatin space . First documented in HeLa cells, where there are generally 10-30 per nucleus, paraspeckles are now known to also exist in all human primary cells,...
s are irregularly shaped compartments in the nucleus' interchromatin space. First documented in HeLa cells, where there are generally 10–30 per nucleus, paraspeckles are now known to also exist in all human primary cells, transformed cell lines and tissue sections. Their name is derived from their distribution in the nucleus; the "para" is short for parallel and the "speckles" refers to the splicing speckles to which they are always in close proximity.
Paraspeckles are dynamic structures that are altered in response to changes in cellular metabolic activity. They are transcription dependent and in the absence of RNA Pol II transcription, the paraspeckle disappears and all of its associated protein components (PSP1, p54nrb, PSP2, CFI(m)68 and PSF) form a crescent shaped perinucleolar cap in the
nucleolusThe nucleolus is a non-membrane bound structure composed of proteins and nucleic acids found within the nucleus. Ribosomal RNA is transcribed and assembled within the nucleolus...
. This phenomenon is demonstrated during the cell cycle. In the
cell cycleThe cell cycle, or cell-division cycle, is the series of events that take place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
, paraspeckles are present during
interphaseInterphase is the phase of the cell cycle in which the cell spends the majority of its time and performs the majority of its purposes including preparation for cell division. In preparation for cell division it increases its size and number of organelles, and makes a copy of its DNA...
and during all of
mitosisMitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets in two daughter nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two daughter cells containing...
except for
telophaseTelophase, from the ancient Greek "τελος" and "φασις" , is a stage in either meiosis or mitosis in an eukaryotic cell reversing the effects of prophase and prometaphase events...
. During telophase, when the two daughter nuclei are formed, there is no
RNARibonucleic acid is a biologically important type of molecule that consists of a long chain of nucleotide units. Each nucleotide consists of a nitrogenous base, a ribose sugar, and a phosphate...
Pol II
transcriptionTranscription, or RNA synthesis, is the process of creating an equivalent RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA in the presence of the correct enzymes...
so the protein components instead form a perinucleolar cap.
Splicing speckles
Sometimes referred to as
interchromatin granule clusters or as
splicing-factor compartments, speckles are rich in splicing snRNPs and other splicing proteins necessary for pre-mRNA processing. Because of a cell's changing requirements, the composition and location of these bodies changes according to mRNA transcription and regulation via
phosphorylationPhosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation turns many protein enzymes on and off, causing or preventing the mechanisms of diseases such as cancer and diabetes....
of specific proteins.
Function
The main function of the cell nucleus is to control gene expression and mediate the replication of DNA during the
cell cycleThe cell cycle, or cell-division cycle, is the series of events that take place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
. The nucleus provides a site for genetic
transcriptionTranscription, or RNA synthesis, is the process of creating an equivalent RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA in the presence of the correct enzymes...
that is segregated from the location of
translationTranslation is the first stage of protein biosynthesis . Translation is the production of proteins by decoding mRNA produced in transcription. Translation occurs in the cytoplasm where the ribosomes are located. Ribosomes are made of a small and large subunit which surrounds the mRNA...
in the cytoplasm, allowing levels of gene regulation that are not available to
prokaryoteThe prokaryotes are a group of organisms that lack a cell nucleus , or any other membrane-bound organelles. They differ from the eukaryotes, which have a cell nucleus. Most are unicellular, but a few prokaryotes such as myxobacteria have multicellular stages in their life cycles...
s.
Cell compartmentalization
The nuclear envelope allows the nucleus to control its contents, and separate them from the rest of the cytoplasm where necessary. This is important for controlling processes on either side of the nuclear membrane. In some cases where a cytoplasmic process needs to be restricted, a key participant is removed to the nucleus, where it interacts with transcription factors to downregulate the production of certain enzymes in the pathway. This regulatory mechanism occurs in the case of
glycolysisGlycolysis is the metabolic pathway that converts glucose, C
6H
12O
6, into pyruvate, C
3H
6O
3-...
, a cellular pathway for breaking down
glucoseGlucose , a monosaccharide also known as - grape sugar, blood sugar, or corn sugar, is a very important carbohydrate in biology. The living cell uses it as a source of energy and metabolic intermediate...
to produce energy.
HexokinaseA hexokinase is an enzyme that phosphorylates a six-carbon sugar, a hexose, to a hexose phosphate. In most tissues and organisms, glucose is the most important substrate of hexokinases, and glucose-6-phosphate the most important product....
is an enzyme responsible for the first the step of glycolysis, forming
glucose-6-phosphateGlucose 6-phosphate is glucose sugar phosphorylated on carbon 6. This compound is very common in cells as the vast majority of glucose entering a cell will become phosphorylated in this way....
from glucose. At high concentrations of fructose-6-phosphate, a molecule made later from glucose-6-phosphate, a regulator protein removes hexokinase to the nucleus, where it forms a transcriptional repressor complex with nuclear proteins to reduce the expression of genes involved in glycolysis.
In order to control which genes are being transcribed, the cell separates some
transcription factorIn the field of molecular biology, a transcription factor is a protein that binds to specific DNA sequences and thereby controls the transfer of genetic information from DNA to mRNA...
proteins responsible for regulating gene expression from physical access to the DNA until they are activated by other signaling pathways. This prevents even low levels of inappropriate gene expression. For example in the case of NF-κB-controlled genes, which are involved in most
inflammatoryInflammation is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. Inflammation is not a...
responses, transcription is induced in response to a
signal pathwayCell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...
such as that initiated by the signaling molecule TNF-α, binds to a cell membrane receptor, resulting in the recruitment of signalling proteins, and eventually activating the transcription factor NF-κB. A nuclear localisation signal on the NF-κB protein allows it to be transported through the nuclear pore and into the nucleus, where it stimulates the transcription of the target genes.
The compartmentalization allows the cell to prevent translation of unspliced mRNA. Eukaryotic mRNA contains introns that must be removed before being translated to produce functional proteins. The splicing is done inside the nucleus before the mRNA can be accessed by ribosomes for translation. Without the nucleus ribosomes would translate newly transcribed (unprocessed) mRNA resulting in misformed and nonfunctional proteins.
Gene expression
Gene expression first involves
transcriptionTranscription, or RNA synthesis, is the process of creating an equivalent RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA in the presence of the correct enzymes...
, in which DNA is used as a template to produce RNA. In the case of genes encoding proteins, that RNA produced from this process is
messenger RNAMessenger ribonucleic acid is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino...
(mRNA), which then needs to be
translatedTranslation is the first stage of protein biosynthesis . Translation is the production of proteins by decoding mRNA produced in transcription. Translation occurs in the cytoplasm where the ribosomes are located. Ribosomes are made of a small and large subunit which surrounds the mRNA...
by ribosomes to form a protein. As ribosomes are located outside the nucleus, mRNA produced needs to be exported.
Since the nucleus is the site of transcription, it also contains a variety of proteins which either directly mediate transcription or are involved in regulating the process. These proteins include
helicaseHelicases are a class of enzymes vital to all living organisms. They are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separating two annealed nucleic acid strands Helicases are a class of enzymes vital to all living organisms. They are motor proteins that...
s that unwind the double-stranded DNA molecule to facilitate access to it,
RNA polymeraseRNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...
s that synthesize the growing RNA molecule,
topoisomeraseTopoisomerases are enzymes that unwind and wind DNA, in order for DNA to control the synthesis of proteins, and in order for DNA to reproduce. They cut the DNA, and at the end of the process connect it again....
s that change the amount of supercoiling in DNA, helping it wind and unwind, as well as a large variety of
transcription factorIn the field of molecular biology, a transcription factor is a protein that binds to specific DNA sequences and thereby controls the transfer of genetic information from DNA to mRNA...
s that regulate expression.
Processing of pre-mRNA
Newly synthesized mRNA molecules are known as
primary transcriptA primary transcript is an RNA molecule that has not yet undergone any modification after its synthesis. For example, a precursor messenger RNA is a primary transcript that becomes a messenger RNA after processing, and a primary microRNA transcript becomes a microRNA after processing....
s or pre-mRNA. They must undergo
post-transcriptional modificationPost-transcriptional modification is a process in cell biology by which, in eukaryotic cells, primary transcript RNA is converted into mature RNA. A notable example is the conversion of precursor messenger RNA into mature messenger RNA , which includes splicing and occurs prior to protein synthesis...
in the nucleus before being exported to the cytoplasm; mRNA that appears in the nucleus without these modifications is degraded rather than used for protein
translationTranslation is the first stage of protein biosynthesis . Translation is the production of proteins by decoding mRNA produced in transcription. Translation occurs in the cytoplasm where the ribosomes are located. Ribosomes are made of a small and large subunit which surrounds the mRNA...
. The three main modifications are
5' capThe 5' cap is a specially altered nucleotide on the 5' end of precursor messenger RNA and some other primary RNA transcripts as found in eukaryotes and, as a special exception, caliciviruses such as noroviruses. The process of 5' capping is vital to creating mature messenger RNA, which is then able...
ping, 3'
polyadenylationPolyadenylation is the addition of a poly tail to an RNA molecule. The poly tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA which only has As. In eukaryotes, polyadenylation is part of the process that produces mature messenger RNA for translation...
, and RNA splicing. While in the nucleus, pre-mRNA is associated with a variety of proteins in complexes known as
heterogeneous ribonucleoprotein particleHeterogeneous nuclear ribonucleoproteins are complexes of RNA and protein present in the cell nucleus during gene transcription and subsequent post-transcriptional modification of the newly synthesized RNA . The presence of the proteins bound to a pre-mRNA molecule serves as a signal that the...
s (hnRNPs). Addition of the 5' cap occurs co-transcriptionally and is the first step in post-transcriptional modification. The 3' poly-
adenineAdenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and protein synthesis, as a chemical component of DNA...
tail is only added after transcription is complete.
RNA splicing, carried out by a complex called the
spliceosomeA spliceosome is a complex of specialized RNA and protein subunits that removes introns from a transcribed pre-mRNA segment. This process is generally referred to as splicing.-Composition:...
, is the process by which introns, or regions of DNA that do not code for protein, are removed from the pre-mRNA and the remaining
exonAn exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule after either portions of a precursor RNA have been removed by cis-splicing or by two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA or...
s connected to re-form a single continuous molecule. This process normally occurs after 5' capping and 3' polyadenylation but can begin before synthesis is complete in transcripts with many exons. Many pre-mRNAs, including those encoding
antibodiesAntibodies are gamma globulin proteins that are found in blood or other bodily fluids of vertebrates, and are used by the immune system to identify and neutralize foreign objects, such as bacteria and viruses...
, can be spliced in multiple ways to produce different mature mRNAs that encode different
protein sequencesIn biochemistry, the primary structure of a biological molecule is the exact specification of its atomic composition and the chemical bonds connecting those atoms...
. This process is known as
alternative splicingAlternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...
, and allows production of a large variety of proteins from a limited amount of DNA.
Nuclear transport
The entry and exit of large molecules from the nucleus is tightly controlled by the nuclear pore complexes. Although small molecules can enter the nucleus without regulation, macromolecules such as RNA and proteins require association
karyopherinKaryopherins are a group of proteins involved in transporting molecules through the pores of the nuclear envelope ....
s called
importinImportin is a type of protein that moves other protein molecules into the nucleus by binding to a specific recognition sequence, called the nuclear localization signal . Importin is classified as a karyopherin....
s to enter the nucleus and exportins to exit. "Cargo" proteins that must be translocated from the cytoplasm to the nucleus contain short amino acid sequences known as
nuclear localization signalA nuclear localization signal or sequence is an amino acid sequence which acts like a 'tag' on the exposed surface of a protein. This sequence is used to target the protein to the cell nucleus through the Nuclear Pore Complex and to direct a newly synthesized protein into the nucleus via its...
s which are bound by importins, while those transported from the nucleus to the cytoplasm carry
nuclear export signalA nuclear export signal is a short amino acid sequence of 5-6 hydrophobic residues in a protein that targets it for export from the cell nucleus to the cytoplasm through the nuclear pore complex. It has the opposite effect of a nuclear localization signal, which targets a protein located in the...
s bound by exportins. The ability of importins and exportins to transport their cargo is regulated by
GTPaseGTPases are a large family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate . The GTP binding and hydrolysis takes place in the highly conserved G domain common to all GTPases.-Functions:...
s, enzymes that hydrolyze the molecule
guanosine triphosphateGuanosine-5'-triphosphate is a purine nucleotide. It can act as a substrate for the synthesis of RNA during transcription process...
to release energy. The key GTPase in nuclear transport is
RanRan is a small 25Kda protein that is involved in transport into and out of the cell nucleus during interphase and also involved in mitosis. It is a member of the Ras superfamily....
, which can bind either GTP or GDP (guanosine diphosphate) depending on whether it is located in the nucleus or the cytoplasm. Whereas importins depend on RanGTP to dissociate from their cargo, exportins require RanGTP in order to bind to their cargo.
Nuclear import depends on the importin binding its cargo in the cytoplasm and carrying it through the nuclear pore into the nucleus. Inside the nucleus, RanGTP acts to separate the cargo from the importin, allowing the importin to exit the nucleus and be reused. Nuclear export is similar, as the exportin binds the cargo inside the nucleus in a process facilitated by RanGTP, exits through the nuclear pore, and separates from its cargo in the cytoplasm.
Specialized export proteins exist for translocation of mature mRNA and tRNA to the cytoplasm after post-transcriptional modification is complete. This quality-control mechanism is important due to the these molecules' central role in protein translation; mis-expression of a protein due to incomplete excision of exons or mis-incorporation of amino acids could have negative consequences for the cell; thus incompletely modified RNA that reaches the cytoplasm is degraded rather than used in translation.
Assembly and disassembly
During its lifetime a nucleus may be broken down, either in the process of
cell divisionCell division is a process by which a cell, called the parent cell, divides into two or more cells, called daughter cells. Cell division is usually a small segment of a larger cell cycle. This type of cell division in eukaryotes is known as mitosis, and leaves the daughter cell capable of dividing...
or as a consequence of
apoptosisApoptosis is the process of programmed cell death that may occur in multicellular organisms. Programmed cell death involves a series of biochemical events leading to a characteristic cell morphology and death; in more specific terms, a series of biochemical events that lead to a variety of...
, a regulated form of cell death. During these events, the structural components of the nucleus—the envelope and lamina—are systematically degraded.
During the
cell cycleThe cell cycle, or cell-division cycle, is the series of events that take place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
the cell divides to form two cells. In order for this process to be possible, each of the new daughter cells must have a full set of genes, a process requiring replication of the chromosomes as well as segregation of the separate sets. This occurs by the replicated chromosomes, the sister chromatids, attaching to
microtubuleMicrotubules are one of the components of the cytoskeleton. They have a diameter of 25 nm and length varying from 200 nanometers to 25 micrometers. Microtubules serve as structural components within cells and are involved in many cellular processes including mitosis, cytokinesis, and vesicular...
s, which in turn are attached to different
centrosomeIn cell biology, the centrosome is an organelle that serves as the main microtubule organizing center of the animal cell as well as a regulator of cell-cycle progression. It was discovered by Edouard Van Beneden in 1883...
s. The sister chromatids can then be pulled to separate locations in the cell. In many cells the centrosome is located in the cytoplasm, outside the nucleus, the microtubules would be unable to attach to the chromatids in the presence of the nuclear envelope. Therefore the early stages in the cell cycle, beginning in
prophaseProphase is a stage of mitosis in which the chromatin condenses into a highly ordered structure called a chromosome in which the chromatin becomes visible. Prophase accounts for approximately 3% of the cell cycle. This process, called chromatin condensation, is mediated by the condensin complex...
and until around
prometaphasePrometaphase is the phase of mitosis following prophase and preceding metaphase, in eukaryotic somatic cells.The nuclear envelope breaks into fragments and disappears. Microtubules emerging from the centrosomes at the poles of the spindle reach the chromosomes, now highly condensed. At the...
, the nuclear membrane is dismantled. Likewise, during the same period, the nuclear lamina is also disassembled, a process regulated by phosphorylation of the lamins. Towards the end of the cell cycle, the nuclear membrane is reformed, and around the same time, the nuclear lamina are reassembled by dephosphorylating the lamins.
However, in dinoflagellates the nuclear envelope remains intact, the centrosomes are located in the cytoplasm, and the microtubules come in contact with chromosomes, whose centromeric regions are incorporated into the nuclear envelope (the so-called closed mitosis with extranuclear spindle). In many other protists (e.g. ciliates, sporozoans) and fungi the centrosomes are intranuclear, and their nuclear envelope also does not disassemle during cell division.
ApoptosisApoptosis is the process of programmed cell death that may occur in multicellular organisms. Programmed cell death involves a series of biochemical events leading to a characteristic cell morphology and death; in more specific terms, a series of biochemical events that lead to a variety of...
is a controlled process in which the cell's structural components are destroyed, resulting in death of the cell. Changes associated with apoptosis directly affect the nucleus and its contents, for example in the condensation of chromatin and the disintegration of the nuclear envelope and lamina. The destruction of the lamin networks is controlled by specialized apoptotic
proteaseA protease breaks down proteins. A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein...
s called
caspaseCaspases, or cysteine-aspartic proteases, are a family of cysteine proteases, which play essential roles in apoptosis , necrosis and inflammation....
s, which cleave the lamin proteins and thus degrade the nucleus' structural integrity. Lamin cleavage is sometimes used as a laboratory indicator of caspase activity in
assayAn assay is a procedure in molecular biology for testing and/or measuring the activity of a drug or biochemical in an organism or organic sample. A quantitative assay may also measure the amount of a substance in a sample. Bioassays and immunoassays are among the many varieties of specialized...
s for early apoptotic activity. Cells that express mutant caspase-resistant lamins are deficient in nuclear changes related to apoptosis, suggesting that lamins play a role in initiating the events that lead to apoptotic degradation of the nucleus. Inhibition of lamin assembly itself is an inducer of apoptosis.
The nuclear envelope acts as a barrier that prevents both DNA and RNA viruses from entering the nucleus. Some viruses require access to proteins inside the nucleus in order to replicate and/or assemble. DNA viruses, such as herpesvirus replicate and assemble in the cell nucleus, and exit by budding through the inner nuclear membrane. This process is accompanied by disassembly of the lamina on the nuclear face of the inner membrane.
Anucleated and polynucleated cells
Although most cells have a single nucleus, some eukaryotic cell types have no nucleus, and others have many nuclei. This can be a normal process, as in the maturation of mammalian
red blood cellRed blood cells are the most common type of blood cell and the vertebrate body's principal means of delivering oxygen to the body tissues via the blood. They take up oxygen in the lungs or gills and release it while squeezing through the body's capillaries. The cells are filled with hemoglobin, a...
s, or a result of faulty cell division.
Anucleated cells contain no nucleus and are therefore incapable of dividing to produce daughter cells. The best-known anucleated cell is the mammalian red blood cell, or erythrocyte, which also lacks other organelles such as mitochondria and serves primarily as a transport vessel to ferry
oxygenOxygen Oxygen Oxygen (acid, literally "sharp", from the taste of acids) and -γενής (-genēs) (producer, literally begetter) is the element with atomic number 8 and represented by the symbol O...
from the lungs to the body's tissues. Erythrocytes mature through
erythropoiesisErythropoiesis is the process by which red blood cells are produced and it is caused by iron released when a red blood cell dies. In human adults, this usually occurs within the bone marrow. In the early fetus, erythropoiesis takes place in the mesodermal cells of the yolk sac. By the third or...
in the
bone marrowBone marrow is the flexible tissue found in the hollow interior of bones. In adults, marrow in large bones produces new blood cells. It constitutes 4% of total body weight, i.e...
, where they lose their nuclei, organelles, and ribosomes. The nucleus is expelled during the process of differentiation from an erythroblast to a
reticulocyteReticulocytes are immature red blood cells, typically composing about 1% of the red cells in the human body.Reticulocytes develop and mature in the red bone marrow and then circulate for about a day in the blood stream before developing into mature red blood cells. Like mature red blood cells,...
, which is the immediate precursor of the mature erythrocyte. The presence of
mutagenIn biology, a mutagen is a physical or chemical agent that changes the genetic material of an organism and thus increases the frequency of mutations above the natural background level. As many mutations cause cancer, mutagens are typically also carcinogens...
s may induce the release of some immature "micronucleated" erythrocytes into the bloodstream. Anucleated cells can also arise from flawed cell division in which one daughter lacks a nucleus and the other has two nuclei.
Polynucleated cells contain multiple nuclei. Most
AcanthareaThe Acantharea are a group of radiolarian protozoa, distinguished mainly by their skeletons.-Structure:These are composed of strontium sulfate crystals, which do not fossilize, and take the form of either ten diametric or twenty radial spines...
n species of
protozoaProtozoa or Cornelius protozoans Protozoa or Cornelius protozoans Protozoa or Cornelius protozoans (from Greek πρῶτον proton "first" and ζῷα zoa "animals"; singular protozoon; (the word "protozoan" is originally an adjective, used as a noun) are microorganisms classified as unicellular eukaryotes....
and some fungi in mycorrhizae have naturally polynucleated cells. Other examples include the intestinal parasites in the genus
GiardiaGiardia is a genus of anaerobic flagellated protozoan parasites of the phylum Metamonada in the supergroup "Excavata" that colonise and reproduce in the small intestines of several vertebrates, causing giardiasis. Their life cycle alternates between an actively swimming trophozoite and an...
, which have two nuclei per cell. In humans,
skeletal muscleSkeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system. It is one of three major muscle types, the others being cardiac and smooth muscle. As its name suggests, skeletal muscle is linked to bone by bundles of collagen fibers known as...
cells, called
myocyteA myocyte is the type of cell found in muscles. They arise from myoblasts.Each myocyte contains myofibrils, which are long chains of sarcomeres, the contractile units of the cell....
s, become polynucleated during development; the resulting arrangement of nuclei near the periphery of the cells allows maximal intracellular space for myofibrils. Multinucleated cells can also be abnormal in humans; for example, cells arising from the fusion of
monocyteMonocyte is a type of white blood cell, part of the human body's immune system. Monocytes have two main functions in the immune system: replenish resident macrophages and dendritic cells under normal states, and in response to inflammation signals, monocytes can move quickly Monocyte is a type of...
s and
macrophageMacrophages are white blood cells within tissues, produced by the division of monocytes. Human macrophages are about in diameter...
s, known as giant multinucleated cells, sometimes accompany inflammation and are also implicated in tumor formation.
Evolution
As the major defining characteristic of the eukaryotic cell, the nucleus'
evolutionIn biology, evolution is change in the genetic material of a population of organisms from one generation to the next. Though changes produced in any one generation are normally small, differences accumulate with each generation and can, over time, cause substantial changes in the population, a...
ary origin has been the subject of much speculation. Four major theories have been proposed to explain the existence of the nucleus, although none have yet earned widespread support.
The theory known as the "syntrophic model" proposes that a
symbioticThe term symbosis commonly describes close and often long-term interactions between different biological species...
relationship between the
archaeaThe Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon . They have no cell nucleus or any other organelles within their cells...
and
bacteriaThe bacteria are a large group of unicellular microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
created the nucleus-containing eukaryotic cell. It is hypothesized that the symbiosis originated when ancient archaea, similar to modern
methanogenicMethanogenesis or biomethanation is the formation of methane by microbes known as methanogens. Organisms capable of producing methane have been identified only from the kingdom Archaea, a group phylogenetically distinct from both eukaryotes and bacteria, although many live in close association with...
archaea, invaded and lived within bacteria similar to modern
myxobacteriaThe myxobacteria are a group of bacteria that predominantly live in the soil. The myxobacteria have very large genomes, relative to other bacteria, e.g. 9-10 million nucleotides. Sorangium cellulosum has the largest known bacterial genome, at 13.0 million nucleotides...
, eventually forming the early nucleus. This theory is analogous to the accepted theory for the origin of eukaryotic mitochondria and
chloroplastChloroplasts are organelles found in plant cells and other eukaryotic organisms that conduct photosynthesis. Chloroplasts capture light energy to conserve free energy in the form of ATP and reduce NADP to NADPH through a complex set of processes called photosynthesis.The word chloroplast is...
s, which are thought to have developed from a similar endosymbiotic relationship between proto-eukaryotes and aerobic bacteria. The archaeal origin of the nucleus is supported by observations that archaea and eukarya have similar genes for certain proteins, including
histoneIn biology, histones are strongly alkaline proteins found in eukaryotic cell nuclei, which package and order the DNA into structual units called nucleosomes. They are the chief protein components of chromatin, act as spools around which DNA winds, and play a role in gene regulation. Without...
s. Observations that myxobacteria are motile, can form multicellular complexes, and possess
kinaseIn chemistry and biochemistry, a kinase, alternatively known as a phosphotransferase, is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates. The process is referred to as phosphorylation...
s and
G proteinG proteins, short for guanine nucleotide-binding proteins, are a family of proteins involved in second messenger cascades.G proteins are so called because they function as "molecular switches," alternating between an inactive guanosine diphosphate and active guanosine triphosphate bound state,...
s similar to eukarya, support a bacterial origin for the eukaryotic cell.
A second model proposes that proto-eukaryotic cells evolved from bacteria without an endosymbiotic stage. This model is based on the existence of modern
planctomycetesPlanctomycetes are a phylum of aquatic bacteria and are found in field samples of brackish, and marine and fresh water samples. They reproduce by budding...
bacteria that possess a nuclear structure with primitive pores and other compartmentalized membrane structures. A similar proposal states that a eukaryote-like cell, the chronocyte, evolved first and phagocytosed archaea and bacteria to generate the nucleus and the eukaryotic cell.
The most controversial model, known as
viral eukaryogenesisViral eukaryogenesis is the hypothesis that the cell nucleus of eukaryotic life forms evolved from a large DNA virus in a form of endosymbiosis within an archaea cell, being a form of symbiogenesis...
, posits that the membrane-bound nucleus, along with other eukaryotic features, originated from the infection of a prokaryote by a virus. The suggestion is based on similarities between eukaryotes and viruses such as linear DNA strands, mRNA capping, and tight binding to proteins (analogizing
histoneIn biology, histones are strongly alkaline proteins found in eukaryotic cell nuclei, which package and order the DNA into structual units called nucleosomes. They are the chief protein components of chromatin, act as spools around which DNA winds, and play a role in gene regulation. Without...
s to
viral envelopeMany viruses have viral envelopes covering their protein capsids. The envelopes typically are derived from portions of the host cell membranes , but include some viral glycoproteins. Functionally, viral envelopes are used to help viruses enter host cells...
s). One version of the proposal suggests that the nucleus evolved in concert with
phagocytosisPhagocytosis is the cellular process of phagocytes and protists of engulfing solid particles by the cell membrane to form an internal phagosome...
to form an early cellular "predator". Another variant proposes that eukaryotes originated from early
archaeaThe Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon . They have no cell nucleus or any other organelles within their cells...
infected by poxviruses, on the basis of observed similarity between the
DNA polymeraseA DNA polymerase is an enzyme that catalyzes the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best-known for their role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand...
s in modern poxviruses and eukaryotes. It has been suggested that the unresolved question of the
evolution of sexScientists currently have developed several competing hypotheses to explain the evolution of sexual reproduction. Many groups of organisms, notably the majority of animals and plants, reproduce sexually. The evolution of sex contains two related, yet distinct, themes: its origin and its maintenance...
could be related to the viral eukaryogenesis hypothesis.
Finally, a very recent proposal suggests that traditional variants of the endosymbiont theory are insufficiently powerful to explain the origin of the eukaryotic nucleus. This model, termed the
exomembrane hypothesis, suggests that the nucleus instead originated from a single ancestral cell that evolved a second exterior cell membrane; the interior membrane enclosing the original cell then became the nuclear membrane and evolved increasingly elaborate pore structures for passage of internally synthesized cellular components such as
ribosomalRibosomes are complexes of RNA and protein that are found in all cells. The ribosome is part of the mechanism that translates the DNA sequence into the protein sequence. Ribosomes from bacteria, archaea and eukaryotes , have significantly different structure and RNA...
subunits.
Further reading
- A review article about nuclear lamins, explaining their structure and various roles
- A review article about nuclear transport, explains the principles of the mechanism, and the various transport pathways
- A review article about the nucleus, explaining the structure of chromosomes within the organelle, and describing the nucleolus and other subnuclear bodies
- A review article about the evolution of the nucleus, explaining a number of different theories
- A university level textbook focusing on cell biology. Contains information on nucleus structure and function, including nuclear transport, and subnuclear domains
External links