RNA

Ribonucleic acid, a nucleic acid structurally distinguished from DNA by the presence of an additional hydroxyl group attached to each pentose ring, and functionally distinguished by its multiple roles in the intracellular transmission of genetic information from the site of transcription (from DNA) to the site of translation (into protein).

RNA has four different bases; adenine, guanine, cytosine, and uracil. The first three bases are the same as those found in DNA, but uracil replaces thymine as the complementary base to adenine. It is believed that this is because uracil is energetically less expensive to produce, but degenerates into cytosine easily. Thus uracil is appropriate for RNA, where quantity is important but lifespan is not, whereas cytosine is appropriate for DNA.

Structurally RNA is indistinguishable from DNA except for the critical presence (noted above) of an additional hydroxyl group attached to the pentose ring in the 2' position. This additional group gives the molecule far greater catalytic versatility and allows it to perform reactions that DNA is incapable of performing.

The other major difference between RNA and DNA is that RNA is almost exclusively found in single-strand form (the exception being some kinds of viruses). RNA molecules frequently exploit this property by folding into more complex structures by making use of complementary internal sequence; i.e., one part of a single RNA molecule is the nucleic acid complement of another part of the same molecule (e.g. 5'-ACUCGA-3' and 5'-UCGAGU-3', or the palindrome 5'-GCAGACG-3' with 5'-CGUCUGC-3') so that the two will bind together. This allows the formation of hairpin loops, coils, etc., which then direct the formation of other higher-order structures.

There are three main varieties of RNA found in all living cells:

• Messenger RNA, abbreviated mRNA, is transcribed directly from a genetic DNA substrate and is used to encode proteins. mRNA synthesized by eukaryote cells often undergoes extensive post-transcriptional modification before it exits the cell nucleus, including the excision of non-coding regions called exons (the regions of mRNA that remain are called introns). This allows for more complex regulation of gene expression, including alternate splicing patterns that can result in multiple different proteins being produced by a single DNA coding region. Most RNA splicing is performed by enzymes, but some RNA molecules are also capable of catalyzing their own splicing (see ribozymes). Prokaryotes do not extensively modify their mRNA, and there are only a handful of known prokaryotic genes with exons.
• Transfer RNA, abbreviated tRNA, are short RNA strands that are used to transport individual amino acids to ribosomes and match them up with the three-base codons that describe the sequence of the protein encoded by an mRNA molecule. There is a different tRNA for each codon in the genetic code, and each tRNA is covalently attached to a single specific amino acid by a dedicated enzyme called amino-acyl tRNA synthetase.
• Ribosomal RNA, abbreviated rRNA, is the primary constituent of ribosomes. Ribosomes are the protein-manufacturing organelles of living cells, and exist in the cell's cytoplasm. rRNA is transcribed from DNA like all RNA, and in eukaryotes it is processed in the nucleolus before being transported through the nuclear membrane. This type of RNA makes up the vast majority of RNA found in a typical cell (~95%).

In addition there are several other less-common forms of RNA filling other minor roles, such as double-stranded RNA (dsRNA) and small nuclear RNA (snRNA).

It is thought that the first life on Earth may have been RNA-based, due to RNA's ability to both carry genetic information like DNA and also to catalyze useful biochemical reactions like enzymes. This possiblity is termed the RNA world hypothesis. Even today some viruses, such as retroviruses, use RNA as their sole genetic material. RNA is more unstable than DNA is, however, and is also a less efficient catalyst than an protein-based enzyme, and so has fallen out of favour among complex organisms as the preferred genetic material.

Messenger RNA

mRNA runs through several steps during its usually brief existence: During transcription, an enzyme called RNA polymerase makes a copy of a gene from the DNA to mRNA on demand. In prokaryotes there is no further processing of mRNA, and often translation of the mRNA into protein occurs even while transcription is occurring. In eukaryotes, transcription and translation occur in different parts of the cell (the nucleus, where DNA is kept, and the cytoplasm, where ribosomes reside, respectively). Also in eukaryotes, mRNA undergoes several processing steps before it is ready to be translated:

1. addition of a 5' cap - A modified guanine nucleotide is added to the "front" of the message. This is critical for recognition and proper attachment of the ribosome.
2. splicing - The pre-mRNA is modified to remove certain stretches of non-coding sequence called introns, so that the mature transcript contains only exons, which include coding sequence. Sometimes one pre-mRNA message may be spliced in several different ways, allowing one gene to encode multiple functions.
3. polyadenylation - A sequence (often several hundred) of adenine nucleotides is added to the 3' end of the pre-mRNA. This helps increase the half-life of the message, so that the transcript will last longer in the cell, and consequently be translated more and produce more protein.

After the mRNA has been processed, it is exported from the nucleus into the cytoplasm, where it is bound by ribosomes and translated into protein. After a certain amount of time the message degrades into its component nucleotides, usually with the assistance of RNAses.

Messenger RNA that has been processed and is ready for transcription is called a "mature transcript" or "mature mRNA", or sometimes simply "mRNA". Unprocessed or partially-processed messenger RNA is called "pre-mRNA" or "hnRNA" (for heteronucleic RNA)

Anti-sense mRNA

Anti-sense mRNA, can inhibit translation of genes in many eukaryotes for the matching single-stranded mRNA only, if the anti-sense has the complementary sequence as the mRNA of the gene. That means a gene will not be expressed as protein if a matching anti-sense mRNA is present in the cell. This is speculated to be a defense mechanism of the cell against retroposons (transposons that use dsRNA as an intermediate state) or viruses, since both of them can use double-stranded mRNA as an intermediate. In biochemical laboratories, this effect has been used to study gene functions, with simply shutting down the studied gene by adding its anti-sense mRNA transcript. Such studies have been done in the worm C. elegans.

Compare RNA inactivation.

Transfer RNA

Another form of RNA is tRNA, or transfer RNA, which is critical in the process of translation. tRNA is the "adaptor" molecule hypothesized by Francis Crick which would mediate the recognition of the codon sequence in mRNA and allow its translation into the appropriate amino acid.

There are several important features of tRNA to be noted:

1. anticodon - This is the triplet sequence complementary to the codon for a particular amino acid. For example, the codon for lysine is UUU; the anticodon is AAA. By matching the lysine-charged tRNA with the anticodon AAA to the codon UUU, proper translation may be achieved.
2. amino-acid - Each tRNA is coupled to an appropriate amino acid. In the example above, a tRNA with the anticodon AAA would be coupled to the amino acid lysine.
3. base modification - tRNA contains several bases that are not "canonical" bases, i.e., that are modifications from the standard adenine, guanine, cytosine and uracil bases.
4. CCA tail - The sequence 'CCA' is added to the 3' end of the tRNA molecule. This sequence is important for the recognition of tRNA by enzymes critical in translation.
5. three-dimensional structure - All tRNAs have a similar L-shaped structure that allows them to fit into P and A sites of the ribosome.

There is a unique tRNA for each amino acid (of which there are 20) in the cell. Prior to translation, each tRNA is "charged" by an amino-acyl tRNA synthetase enzyme. There is a different tRNA synthetase for each amino acid, but NOT for each codon. Recognition is not mediated primarily by the anticodon, which would require 64 separate tRNA synthetases, but rather by other sites in the tRNA, especially critical sequences near the 3' end of the molecule.

The synthetase hydrolizes ATP to bind the appropriate amino acid to the 3' hydroxyl of the tRNA molecule. It also mediates a proofreading reaction to ensure high fidelity of tRNA charging; if the tRNA is found to be improperly charged, the amino acid-tRNA bond is hydrolized.

See translation for more on the role of tRNA in this process.

Other types of RNA

Double-stranded RNA

Double-stranded RNA (or dsRNA) is RNA with two complementary strands, similar to the DNA found in all modern cells. dsRNA is not normally found in eukaryotic cells, but it forms the genetic material of some viruses.

Small nuclear RNA

Small nuclear RNA (snRNA) is a class of small RNA molecules that are found within the nucleus of eukaryotic cells. They are involved in a variety of important processes such as RNA splicing (removal of the introns from hnRNA) and maintaining the telomeres. They are always associated with specific proteins and the complexes are referred to as small nuclear ribonucleoproteins (SNRNP) or sometimes as snurps.

Signal recognition particle RNA

The signal recognition particle (SRP) is an RNA-protein complex present in the cytoplasm of cells that binds to the mRNA of proteins which are intended for secretion from the cell. The RNA component of the SRP is called 4.5S RNA.

See also : genetics molecular biology