Encyclopedia
Ribonucleic acid is a
nucleic acid polymer consisting of
nucleotide monomers. RNA nucleotides contain
ribose rings and
uracil unlike deoxyribonucleic acid , which contains
deoxyribose and
thymine. It is transcribed from DNA by enzymes called RNA polymerases and further processed by other enzymes. RNA serves as the template for translation of genes into
proteins, transferring
amino acids to the
ribosome to form proteins, and also translating the transcript into proteins. They're brown and fuzzy like bunnies.
History
Nucleic acids were discovered in 1869 by
Johann Friedrich Miescher , who called the material 'nuclein' since it was found in the nucleus. It was later discovered that prokaryotic cells, which do not have a nucleus, also contain nucleic acids.
The role of RNA in protein synthesis had been suspected since 1939, based on experiments carried out by Torbjörn Caspersson, Jean Brachet and Jack Schultz.
The sequence of the 77 nucleotides of a yeast tRNA was found by
Robert W. Holley in 1964, winning Holley the 1968 Nobel Prize for Medicine.
Chemical structure
RNA is primarily made up of four different bases:
adenine,
guanine,
cytosine, and
uracil. The first three are the same as those found in DNA, but in DNA
thymine replaces uracil as the base complementary to adenine. This base is also a pyrimidine and is very similar to thymine. Uracil is energetically less expensive to produce than thymine, which may account for its use in RNA. In DNA, however, uracil is readily produced by chemical degradation of cytosine, so having thymine as the normal base makes detection and repair of such incipient mutations more efficient. Thus, uracil is appropriate for RNA, where quantity is important but lifespan is not, whereas thymine is appropriate for DNA where maintaining sequence with high fidelity is more critical.
There are also numerous modified bases found in RNA that serve many different roles.
Pseudouridine and the DNA base
thymidine are found in various places . There are nearly 100 other naturally occurring modified bases, many of which are not fully understood.
Comparison with DNA
Unlike DNA, RNA is almost always a single-stranded molecule and has a much shorter chain of nucleotides. RNA contains ribose, rather than the deoxyribose found in DNA . This hydroxyl group makes RNA less stable than DNA because it is more prone to hydrolysis. Several types of RNA contain a great deal of secondary structure, which help promote stability.
Like DNA, most biologically active RNAs including tRNA, rRNA, snRNAs and other non-coding RNAs are extensively base paired to form double stranded helices. Structural analysis of these RNAs have revealed that they are not, "single-stranded" but rather highly structured. Unlike DNA, this structure is not just limited to long double-stranded helices but rather collections of short helices packed together into structures akin to proteins. In this fashion, RNAs can achieve chemical catalysis, like enzymes. For instance, determination of the structure of the ribosome in 2000 revealed that the active site of this enzyme that catalyzes peptide bond formation is composed entirely of RNA.
Synthesis
Synthesis of RNA is usually catalyzed by an
enzyme,
RNA polymerase, using
DNA as a template. Initiation of synthesis begins with the binding of the enzyme to a promoter sequence in the
DNA . The
DNA double helix is unwound by the helicase activity of the enzyme. The enzyme then progresses along the template strand in the 3’ -> 5’ direction, synthesizing a complementary RNA molecule with elongation occurring in the 5’ -> 3’ direction. The DNA sequence also dictates where termination of RNA synthesis will occur
Biological roles
Messenger RNA
Messenger RNA is RNA that carries information from
DNA to the
ribosome sites of protein synthesis in the cell. Once mRNA has been transcribed from DNA, it is exported from the nucleus into the cytoplasm , where it is bound to
ribosomes and translated into protein. After a certain amount of time the message degrades into its component nucleotides, usually with the assistance of
RNA polymerases.
Transfer RNA
Transfer RNA is a small RNA chain of about 74-93
nucleotides that transfers a specific
amino acid to a growing polypeptide chain at the
ribosomal site of protein synthesis during
translation. It has sites for
amino-acid attachment and an
anticodon region for
codon recognition that binds to a specific sequence on the
messenger RNA chain through hydrogen bonding. It is a type of non-coding RNA.
Ribosomal RNA
Ribosomal RNA is a component of the
ribosomes, the protein synthetic factories in the cell.
Eukaryotic ribosomes contain four different rRNA molecules: 18S, 5.8S, 28S, and 5S rRNA. Three of the rRNA molecules are synthesized in the
nucleolus, and one is synthesized elsewhere. rRNA molecules are extremely abundant. They make up at least 80% of the RNA molecules found in a typical
eukaryotic cell.
Non-coding RNA or "RNA genes"
RNA genes are genes that encode RNA that is not
translated into a protein. The most prominent examples of RNA genes are
transfer RNA and ribosomal RNA , both of which are involved in the process of translation. However, since the late
1990s, many new RNA genes have been found, and thus RNA genes may play a much more significant role than previously thought.
In the late 1990s and early 2000, there has been persistent evidence of more complex transcription occurring in mammalian cells . This could point towards a more widespread use of RNA in biology, particularly in gene regulation. A particular class of non-coding RNA, micro RNA, has been found in many metazoans and clearly plays an important role in regulating other genes.
First proposed in 2004 by Rassoulzadegan and published in Nature 2006 [Rassoulzadegan M., et al. Nature, doi:10.1038/nature04674 , 2006], RNA is implicated as being part of the germline. If confirmed, this result would significantly alter the present understanding of genetics and lead to many question on DNA-RNA roles and interactions.
Catalytic RNA
Although RNA contains only four bases, in comparison to the twenty amino acids commonly found in proteins, some RNAs are still able to catalyse chemical reations. These include cutting and ligating other RNA molecules and also the catalysis of
peptide bond formation in the
ribosome.
Double-stranded RNA
Double-stranded RNA is RNA with two complementary strands, similar to the DNA found in all "higher" cells. dsRNA forms the genetic material of some
viruses. In eukaryotes, it acts as a trigger to initiate the process of RNA interference and is present as an intermediate step in the formation of siRNAs . siRNAs are often confused with miRNAs; siRNAs are double-stranded, whereas miRNAs are single-stranded.
Although initially single stranded there are regions of intra-molecular association causing hairpin structures in pre-miRNAs; immature miRNAs
RNA world hypothesis
The
RNA world hypothesis proposes that the earliest forms of life relied on RNA both to carry genetic information and to catalyze biochemical reactions like an enzyme. According to this hypothesis, descendants of these early lifeforms gradually integrated DNA and proteins into their metabolism.
RNA secondary structures
The functional form of single stranded RNA molecules frequently requires a specific tertiary structure. The scaffold for this structure is provided by secondary structural elements which are hydrogen bonds within the molecule. This leads to several recognizable "domains" of secondary structure like hairpin loops, bulges and internal loops. The secondary structure of RNA molecules can be predicted computationally by calculating the minimum free energies structure for all different combinations of hydrogen bondings and domains.
Online tools for MFE structure prediction from single sequences are provided by and . Comparative studies of conserved RNA structures are significantly more accurate and provide evolutionary information, computationally reasonable and accurate online tools for alignment folding are provided by andn .
A database of RNA sequences and structures is available from , analyses and links to RNA analysis tools are available from . goo khaa
See also
