Messenger RNA

Messenger RNA

Overview
Messenger RNA is a molecule of RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

 encoding a chemical "blueprint" for a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 product. mRNA is transcribed
Transcription (genetics)
Transcription is the process of creating a complementary 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 by the action of the correct enzymes...

 from a DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated
Translation (genetics)
In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...

 into a polymer of amino acids: a protein. In mRNA as in DNA, genetic information is encoded in the sequence of nucleotides arranged into codons consisting of three bases
Base (chemistry)
For the term in genetics, see base A base in chemistry is a substance that can accept hydrogen ions or more generally, donate electron pairs. A soluble base is referred to as an alkali if it contains and releases hydroxide ions quantitatively...

 each.
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Encyclopedia
Messenger RNA is a molecule of RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

 encoding a chemical "blueprint" for a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 product. mRNA is transcribed
Transcription (genetics)
Transcription is the process of creating a complementary 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 by the action of the correct enzymes...

 from a DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated
Translation (genetics)
In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...

 into a polymer of amino acids: a protein. In mRNA as in DNA, genetic information is encoded in the sequence of nucleotides arranged into codons consisting of three bases
Base (chemistry)
For the term in genetics, see base A base in chemistry is a substance that can accept hydrogen ions or more generally, donate electron pairs. A soluble base is referred to as an alkali if it contains and releases hydroxide ions quantitatively...

 each. Each codon encodes for a specific amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

, except the stop codon
Stop codon
In the genetic code, a stop codon is a nucleotide triplet within messenger RNA that signals a termination of translation. Proteins are based on polypeptides, which are unique sequences of amino acids. Most codons in messenger RNA correspond to the addition of an amino acid to a growing polypeptide...

s, which terminate protein synthesis. This process requires two other types of RNA: Transfer RNA
Transfer RNA
Transfer RNA is an adaptor molecule composed of RNA, typically 73 to 93 nucleotides in length, that is used in biology to bridge the three-letter genetic code in messenger RNA with the twenty-letter code of amino acids in proteins. The role of tRNA as an adaptor is best understood by...

 (tRNA) mediates recognition of the codon and provides the corresponding amino acid, whereas ribosomal RNA
Ribosomal RNA
Ribosomal ribonucleic acid is the RNA component of the ribosome, the enzyme that is the site of protein synthesis in all living cells. Ribosomal RNA provides a mechanism for decoding mRNA into amino acids and interacts with tRNAs during translation by providing peptidyl transferase activity...

 (rRNA) is the central component of the ribosome's protein-manufacturing machinery.

Synthesis, processing, and function


The brief existence of an mRNA molecule begins with transcription and ultimately ends in degradation. During its life, an mRNA molecule may also be processed, edited, and transported prior to translation. Eukaryotic mRNA molecules often require extensive processing and transport, while prokaryotic molecules do not.

Transcription



Transcription is when DNA makes RNA. During transcription, RNA polymerase
RNA polymerase
RNA 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...

 makes a copy of a gene from the DNA to mRNA as needed. This process is similar in eukaryotes and prokaryotes. One notable difference, however, is that prokaryotic RNA polymerase associates with mRNA-processing enzymes during transcription so that processing can proceed quickly after the start of transcription. The short-lived, unprocessed or partially processed, product is termed pre-mRNA; once completely processed, it is termed mature mRNA.

Eukaryotic pre-mRNA processing



Processing of mRNA differs greatly among eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...

s, bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

, and archea. Non-eukaryotic mRNA is, in essence, mature upon transcription and requires no processing, except in rare cases. Eukaryotic pre-mRNA, however, requires extensive processing.

5' cap addition



A 5' cap (also termed an RNA cap, an RNA 7-methylguanosine cap, or an RNA m7G cap) is a modified guanine nucleotide that has been added to the "front" or 5' end of a eukaryotic messenger RNA shortly after the start of transcription. The 5' cap consists of a terminal 7-methylguanosine residue that is linked through a 5'-5'-triphosphate bond to the first transcribed nucleotide. Its presence is critical for recognition by the ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....

 and protection from RNases.

Cap addition is coupled to transcription, and occurs co-transcriptionally, such that each influences the other. Shortly after the start of transcription, the 5' end of the mRNA being synthesized is bound by a cap-synthesizing complex associated with RNA polymerase
RNA polymerase
RNA 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...

. This enzymatic
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 complex catalyzes the chemical reactions that are required for mRNA capping. Synthesis proceeds as a multi-step biochemical
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...

 reaction.

Splicing



Splicing is the process by which pre-mRNA is modified to remove certain stretches of non-coding sequences called intron
Intron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...

s; the stretches that remain include protein-coding sequences and are called exon
Exon
An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...

s. Sometimes pre-mRNA messages may be spliced in several different ways, allowing a single gene to encode multiple proteins. This process is called alternative splicing
Alternative splicing
Alternative 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...

. Splicing is usually performed by an RNA-protein complex called the spliceosome
Spliceosome
A spliceosome is a complex of snRNA and protein subunits that removes introns from a transcribed pre-mRNA segment. This process is generally referred to as splicing.-Composition:...

, but some RNA molecules are also capable of catalyzing their own splicing (see ribozyme
Ribozyme
A ribozyme is an RNA molecule with a well defined tertiary structure that enables it to catalyze a chemical reaction. Ribozyme means ribonucleic acid enzyme. It may also be called an RNA enzyme or catalytic RNA. Many natural ribozymes catalyze either the hydrolysis of one of their own...

s
).

Editing


In some instances, an mRNA will be edited
RNA editing
The term RNA editing describes those molecular processes in which the information content in an RNA molecule is altered through a chemical change in the base makeup. To date, such changes have been observed in tRNA, rRNA, mRNA and microRNA molecules of eukaryotes but not prokaryotes...

, changing the nucleotide composition of that mRNA. An example in humans is the apolipoprotein B
Apolipoprotein B
Apolipoprotein B is the primary apolipoprotein of low-density lipoproteins , which is responsible for carrying cholesterol to tissues. While it is unclear exactly what functional role APOB plays in LDL, it is the primary apolipoprotein component and is absolutely required for its formation...

 mRNA, which is edited in some tissues, but not others. The editing creates an early stop codon, which, upon translation, produces a shorter protein.

Polyadenylation



Polyadenylation is the covalent linkage of a polyadenylyl moiety to a messenger RNA molecule. In eukaryotic organisms, most messenger RNA (mRNA) molecules are polyadenylated at the 3' end. The poly(A) tail and the protein bound to it aid in protecting mRNA from degradation by exonucleases. Polyadenylation is also important for transcription termination, export of the mRNA from the nucleus, and translation. mRNA can also be polyadenylated in prokaryotic organisms, where poly(A) tails act to facilitate, rather than impede, exonucleolytic degradation.

Polyadenylation occurs during and immediately after transcription of DNA into RNA. After transcription has been terminated, the mRNA chain is cleaved through the action of an endonuclease complex associated with RNA polymerase. After the mRNA has been cleaved, around 250 adenosine residues are added to the free 3' end at the cleavage site. This reaction is catalyzed by polyadenylate polymerase. Just as in alternative splicing, there can be more than one polyadenylation variant of a mRNA.

Transport


Another difference between eukaryotes and prokaryotes is mRNA transport. Because eukaryotic transcription and translation is compartmentally separated, eukaryotic mRNAs must be exported from the nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

 to the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...

. Mature mRNAs are recognized by their processed modifications and then exported through the nuclear pore
Nuclear pore
Nuclear 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...

. In neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s, mRNA must be transported from the soma
Soma (biology)
The soma , or perikaryon , or cyton, is the bulbous end of a neuron, containing the cell nucleus. The word "soma" comes from the Greek σῶμα, meaning "body"; the soma of a neuron is often called the "cell body"...

 to the dendrite
Dendrite
Dendrites are the branched projections of a neuron that act to conduct the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project...

s where local translation occurs in response to external stimuli. Many messages are marked with so-called "zip codes," which target their transport to a specific location.

Translation



Because prokaryotic mRNA does not need to be processed or transported, translation by the ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....

 can begin immediately after the end of transcription. Therefore, it can be said that prokaryotic translation is coupled to transcription and occurs co-transcriptionally.

Eukaryotic mRNA that has been processed and transported to the cytoplasm (i.e., mature mRNA) can then be translated by the ribosome. Translation may occur at ribosomes free-floating in the cytoplasm, or directed to the endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...

 by the signal recognition particle
Signal recognition particle
The signal recognition particle is an abundant, cytosolic, universally conserved ribonucleoprotein that recognizes and targets specific proteins to the endoplasmic reticulum in eukaryotes and the plasma membrane in prokaryotes....

. Therefore, unlike in prokaryotes, eukaryotic translation is not directly coupled to transcription.

Structure



5' cap



The 5' cap is a modified guanine nucleotide added to the "front" (5' end) of the pre-mRNA using a 5'-5'-triphosphate linkage. This modification is critical for recognition and proper attachment of mRNA to the ribosome, as well as protection from 5' exonucleases. It may also be important for other essential processes, such as splicing and transport.

Coding regions



Coding regions are composed of codons, which are decoded and translated (in eukaryotes usually into one and in prokaryotes usually into several) proteins by the ribosome. Coding regions begin with the start codon
Start codon
The start codon is generally defined as the point, sequence, at which a ribosome begins to translate a sequence of RNA into amino acids.When an RNA transcript is "read" from the 5' carbon to the 3' carbon by the ribosome the start codon is the first codon on which the tRNA bound to Met,...

 and end with a stop codon
Stop codon
In the genetic code, a stop codon is a nucleotide triplet within messenger RNA that signals a termination of translation. Proteins are based on polypeptides, which are unique sequences of amino acids. Most codons in messenger RNA correspond to the addition of an amino acid to a growing polypeptide...

. In general, the start codon is an AUG triplet and the stop codon is UAA, UAG, or UGA. The coding regions tend to be stabilised by internal base pairs, this impedes degradation. In addition to being protein-coding, portions of coding regions may serve as regulatory sequences in the pre-mRNA as exonic splicing enhancer
Exonic splicing enhancer
An exonic splicing enhancer is a DNA sequence motif consisting of 6 bases within an exon that directs, or enhances, accurate splicing of hetero-nuclear RNA or pre-mRNA into messenger RNA .- The Basics :...

s or exonic splicing silencer
Exonic splicing silencer
An exonic splicing silencer is a small region of an exon that inhibits or silences splicing of the pre-mRNA....

s.

Untranslated regions


Untranslated regions (UTRs) are sections of the mRNA before the start codon and after the stop codon that are not translated, termed the five prime untranslated region
Five prime untranslated region
A messenger ribonucleic acid molecule codes for a protein through translation. The mRNA also contains regions that are not translated: in eukaryotes these include the 5' untranslated region, 3' untranslated region, 5' cap and poly-A tail....

 (5' UTR) and three prime untranslated region
Three prime untranslated region
In molecular genetics, the three prime untranslated region is a particular section of messenger RNA . It is preceeded by the coding region....

 (3' UTR), respectively. These regions are transcribed with the coding region and thus are exon
Exon
An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...

ic as they are present in the mature mRNA. Several roles in gene expression have been attributed to the untranslated regions, including mRNA stability, mRNA localization, and translational efficiency
Translational efficiency
Translational efficiency, in the context of cell biology, is the rate of mRNA translation into proteins within cells....

. The ability of a UTR to perform these functions depends on the sequence of the UTR and can differ between mRNAs.

The stability of mRNAs may be controlled by the 5' UTR and/or 3' UTR due to varying affinity for RNA degrading enzymes called ribonuclease
Ribonuclease
Ribonuclease is a type of nuclease that catalyzes the degradation of RNA into smaller components. Ribonucleases can be divided into endoribonucleases and exoribonucleases, and comprise several sub-classes within the EC 2.7 and 3.1 classes of enzymes.-Function:All organisms studied contain...

s and for ancillary proteins that can promote or inhibit RNA degradation.

Translational efficiency, including sometimes the complete inhibition of translation, can be controlled by UTRs. Proteins that bind to either the 3' or 5' UTR may affect translation by influencing the ribosome's ability to bind to the mRNA. MicroRNAs bound to the 3' UTR also may affect translational efficiency or mRNA stability.

Cytoplasmic localization of mRNA is thought to be a function of the 3' UTR. Proteins that are needed in a particular region of the cell can also be translated there; in such a case, the 3' UTR may contain sequences that allow the transcript to be localized to this region for translation.

Some of the elements contained in untranslated regions form a characteristic secondary structure
Secondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...

 when transcribed into RNA. These structural mRNA elements are involved in regulating the mRNA. Some, such as the SECIS element
SECIS element
In biology, the SECIS element is an RNA element around 60 nucleotides in length that adopts a stem-loop structure. This structural motif directs the cell to translate UGA codons as selenocysteines...

, are targets for proteins to bind. One class of mRNA element, the riboswitch
Riboswitch
In molecular biology, a riboswitch is a part of an mRNA molecule that can directly bind a small target molecule, and whose binding of the target affects the gene's activity. Thus, an mRNA that contains a riboswitch is directly involved in regulating its own activity, in response to the...

es, directly bind small molecules, changing their fold to modify levels of transcription or translation. In these cases, the mRNA regulates itself.

Poly(A) tail



The 3' poly(A) tail is a long sequence of adenine
Adenine
Adenine 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...

 nucleotides (often several hundred) added to the 3' end of the pre-mRNA. This tail promotes export from the nucleus and translation, and protects the mRNA from degradation.

Monocistronic versus polycistronic mRNA


An mRNA molecule is said to be monocistronic when it contains the genetic information to translate
Translation (genetics)
In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...

 only a single protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 chain (polypeptide). This is the case for most of the eukaryotic
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...

 mRNAs. On the other hand, polycistronic mRNA carries several open reading frame
Open reading frame
In molecular genetics, an open reading frame is a DNA sequence that does not contain a stop codon in a given reading frame.Normally, inserts which interrupt the reading frame of a subsequent region after the start codon cause frameshift mutation of the sequence and dislocate the sequences for stop...

s (ORFs), each of which is translated into a polypeptide. These polypeptides usually have a related function (they often are the subunits composing a final complex protein) and their coding sequence is grouped and regulated together in an operon
Operon
In genetics, an operon is a functioning unit of genomic DNA containing a cluster of genes under the control of a single regulatory signal or promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo trans-splicing to create...

. Most of the mRNA found in bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 and archea is polycistronic. Dicistronic or bicistronic is the term used to describe an mRNA that encodes only two proteins.

mRNA circularization


In eukaryotes it is thought that mRNA molecules form circular structures due to an interaction between the cap binding complex
Cap binding complex
The 5' cap of eukaryotic messenger RNA is bound at all times by various Cap-binding complexes.-Nuclear cap-binding complex:In the nucleus freshly transcribed mRNA molecules are bound on the 5' cap by the nuclear cap-binding complex of Cbc1/Cbc2 in yeast or CBC20/CBC80 in metazoans. These aid in...

 and poly(A)-binding protein
Poly(A)-binding protein
Poly-binding protein is a RNA-binding protein which binds to the poly tail of mRNA. The poly tail is located on the 3' end of mRNA...

. Circularization is thought to promote recycling of ribosomes on the same message leading to efficient translation.

Degradation


Different mRNAs within the same cell have distinct lifetimes (stabilities). In bacterial cells, individual mRNAs can survive from seconds to more than an hour; in mammalian cells, mRNA lifetimes range from several minutes to days. The greater the stability of an mRNA the more protein may be produced from that mRNA. The limited lifetime of mRNA enables a cell to alter protein synthesis rapidly in response to its changing needs. There are many mechanisms that lead to the destruction of a mRNA, some of which are described below.

Prokaryotic mRNA degradation


In general, in prokaryotes the lifetime of mRNA is much shorter than in eukaryotes. Prokaryotes degrade messages by using a combination of ribonucleases, including endonucleases, 3' exonucleases, and 5' exonucleases. In some instances, small RNA molecules (sRNA) tens to hundreds of nucleotides long can stimulate the degradation of specific mRNAs by base-pairing with complementary sequences and facilitating ribonuclease cleavage. It was recently shown that bacteria also have a sort of 5' cap
5' cap
The 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. The process of 5' capping is vital to creating mature messenger RNA, which is then able to undergo translation...

 consisting of a triphosphate on the 5' end. Removal of two of the phosphates leaves a 5' monophosphate, causing the message to be destroyed by the endonuclease
Endonuclease
Endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain, in contrast to exonucleases, which cleave phosphodiester bonds at the end of a polynucleotide chain. Typically, a restriction site will be a palindromic sequence four to six nucleotides long. Most...

 RNase E.

Eukaryotic mRNA turnover


Inside eukaryotic cells, there is a balance between the processes of translation
Translation (genetics)
In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...

 and mRNA decay. Messages that are being actively translated are bound by ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....

s, the eukaryotic initiation factor
Eukaryotic initiation factor
Eukaryotic initiation factors are proteins involved in the initiation phase of eukaryotic translation. They function in forming a complex with the 40S ribosomal subunit and Met-tRNAi called the 43S preinitation complex , recognizing the 5' cap structure of mRNA and recruiting the 43S PIC to mRNA,...

s eIF-4E and eIF-4G, and poly(A)-binding protein
Poly(A)-binding protein
Poly-binding protein is a RNA-binding protein which binds to the poly tail of mRNA. The poly tail is located on the 3' end of mRNA...

. eIF-4E and eIF-4G block the decapping enzyme (DCP2
DCP2
mRNA-decapping enzyme 2 is a protein that in humans is encoded by the DCP2 gene.-Interactions:DCP2 has been shown to interact with DCP1A and UPF1.-Further reading:...

), and poly(A)-binding protein blocks the exosome complex
Exosome complex
The exosome complex is a multi-protein complex capable of degrading various types of RNA molecules...

, protecting the ends of the message. The balance between translation and decay is reflected in the size and abundance of cytoplasmic structures known as P-bodies
P-bodies
Processing bodies were first described in the scientific literature by Bashkirov et. al. in 1997, in which they describe "small granules… discrete, prominent foci" as the cytoplasmic location of the mouse exoribonuclease mXrn1p. It wasn’t until 2002 that a glimpse into the nature and importance of...

  The poly(A) tail
Polyadenylation
Polyadenylation 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 that has only adenine bases. In eukaryotes, polyadenylation is part of the process that produces mature messenger RNA for translation...

 of the mRNA is shortened by specialized exonucleases that are targeted to specific messenger RNAs by a combination of cis-regulatory sequences on the RNA and trans-acting RNA-binding proteins. Poly(A) tail removal is thought to disrupt the circular structure of the message and destabilize the cap binding complex
Cap binding complex
The 5' cap of eukaryotic messenger RNA is bound at all times by various Cap-binding complexes.-Nuclear cap-binding complex:In the nucleus freshly transcribed mRNA molecules are bound on the 5' cap by the nuclear cap-binding complex of Cbc1/Cbc2 in yeast or CBC20/CBC80 in metazoans. These aid in...

. The message is then subject to degradation by either the exosome complex
Exosome complex
The exosome complex is a multi-protein complex capable of degrading various types of RNA molecules...

 or the decapping complex
Decapping complex
The mRNA decapping complex is a protein complex in eukaryotic cells responsible for removal of the 5' cap. The core of the decapping complex is the Nudix family enzyme Dcp2. Many other proteins assemble with Dcp2 to form a protein complex....

. In this way, translationally inactive messages can be destroyed quickly, while active messages remain intact. The mechanism by which translation stops and the message is handed-off to decay complexes is not understood in detail.

AU-rich element decay


The presence of AU-rich element
AU-rich element
AU-rich elements are one of the most common types of regulatory elements found in mRNAs. They are involved in the control of gene expression. They are the most common determinant of RNA stability in mammalian cells....

s in some mammalian mRNAs tends to destabilize those transcripts through the action of cellular proteins that bind these sequences and stimulate poly(A) tail removal. Loss of the poly(A) tail is thought to promote mRNA degradation by facilitating attack by both the exosome complex
Exosome complex
The exosome complex is a multi-protein complex capable of degrading various types of RNA molecules...

 and the decapping complex
Decapping complex
The mRNA decapping complex is a protein complex in eukaryotic cells responsible for removal of the 5' cap. The core of the decapping complex is the Nudix family enzyme Dcp2. Many other proteins assemble with Dcp2 to form a protein complex....

. Rapid mRNA degradation via AU-rich element
AU-rich element
AU-rich elements are one of the most common types of regulatory elements found in mRNAs. They are involved in the control of gene expression. They are the most common determinant of RNA stability in mammalian cells....

s is a critical mechanism for preventing the overproduction of potent cytokines such as tumor necrosis factor (TNF) and granulocyte-macrophage colony stimulating factor (GM-CSF). AU-rich elements also regulate the biosynthesis of proto-oncogenic transcription factors like c-Jun
C-jun
c-Jun is the name of a gene and protein that, in combination with c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the c-jun gene. It is activated through double phosphorylation by the...

 and c-Fos
C-Fos
In the field of molecular biology and Genetics, c-Fos is a protein encoded by the FOS gene.-Structure and function:c-Fos is a cellular proto-oncogene belonging to the immediate early gene family of transcription factors. c-Fos has a leucine-zipper DNA binding domain, and a transactivation domain at...

.

Nonsense mediated decay


Eukaryotic messages are subject to surveillance by nonsense mediated decay
Nonsense mediated decay
Nonsense-mediated decay is a cellular mechanism of mRNA surveillance that functions to detect nonsense mutations and prevent the expression of truncated or erroneous proteins. Following transcription, precursor mRNA undergoes an assemblage of ribonucleoprotein components followed by regulatory...

 (NMD), which checks for the presence of premature stop codons (nonsense codons) in the message. These can arise via incomplete splicing, V(D)J recombination
V(D)J recombination
VJ recombination, also known as somatic recombination, is a mechanism of genetic recombination in the early stages of immunoglobulin and T cell receptors production of the immune system...

 in the adaptive immune system
Adaptive immune system
The adaptive immune system is composed of highly specialized, systemic cells and processes that eliminate or prevent pathogenic growth. Thought to have arisen in the first jawed vertebrates, the adaptive or "specific" immune system is activated by the “non-specific” and evolutionarily older innate...

, mutations in DNA, transcription errors, leaky scanning
Leaky scanning
Leaky scanning is a technique commonly employed by viruses to express multiple proteins from a single sequence of RNA. The nucleotides surrounding the stop codon can disturb the ribosome causing it to shift reading frames and continue to translate past the stop codon...

 by the ribosome causing a frame shift, and other causes. Detection of a premature stop codon triggers mRNA degradation by 5' decapping, 3' poly(A) tail removal, or endonucleolytic cleavage
Endonuclease
Endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain, in contrast to exonucleases, which cleave phosphodiester bonds at the end of a polynucleotide chain. Typically, a restriction site will be a palindromic sequence four to six nucleotides long. Most...

.
and amanda is cool

Small interfering RNA (siRNA)


In metazoans, small interfering RNA
Small interfering RNA
Small interfering RNA , sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA molecules, 20-25 nucleotides in length, that play a variety of roles in biology. The most notable role of siRNA is its involvement in the RNA interference pathway, where it...

s (siRNAs) processed by Dicer
Dicer
Dicer is an endoribonuclease in the RNase III family that cleaves double-stranded RNA and pre-microRNA into short double-stranded RNA fragments called small interfering RNA about 20-25 nucleotides long, usually with a two-base overhang on the 3' end...

 are incorporated into a complex known as the RNA-induced silencing complex
RNA-induced silencing complex
RNA-Induced Silencing Complex, or RISC, is a multiprotein complex that incorporates one strand of a small interfering RNA or micro RNA . RISC uses the siRNA or miRNA as a template for recognizing complementary mRNA. When it finds a complementary strand, it activates RNase and cleaves the RNA...

 or RISC. This complex contains an endonuclease
Endonuclease
Endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain, in contrast to exonucleases, which cleave phosphodiester bonds at the end of a polynucleotide chain. Typically, a restriction site will be a palindromic sequence four to six nucleotides long. Most...

 that cleaves perfectly complementary messages to which the siRNA binds. The resulting mRNA fragments are then destroyed by exonuclease
Exonuclease
Exonucleases are enzymes that work by cleaving nucleotides one at a time from the end of a polynucleotide chain. A hydrolyzing reaction that breaks phosphodiester bonds at either the 3’ or the 5’ end occurs. Its close relative is the endonuclease, which cleaves phosphodiester bonds in the middle ...

s. siRNA is commonly used in laboratories to block the function of genes in cell culture. It is thought to be part of the innate immune system as a defense against double-stranded RNA viruses.

MicroRNA (miRNA)


MicroRNAs (miRNAs) are small RNAs that typically are partially complementary to sequences in metazoan messenger RNAs. Binding of a miRNA to a message can repress translation of that message and accelerate poly(A) tail removal, thereby hastening mRNA degradation. The mechanism of action of miRNAs is the subject of active research.

Other decay mechanisms


There are other ways by which messages can be degraded, including non-stop decay
Non-stop decay
Non-stop decay is a cellular mechanism of mRNA surveillance to detect mRNA molecules lacking a stop codon and prevent these mRNAs from translation. The non-stop decay pathway releases ribosomes that have reached the far 3' end of an mRNA and guides the mRNA to the exosome complex for degradation. -...

 and silencing by Piwi-interacting RNA
Piwi-interacting RNA
Piwi-interacting RNA is the largest class of small non-coding RNA molecules that is expressed in animal cells. piRNAs form RNA-protein complexes through interactions with piwi proteins...

(piRNA), among others.

External links