Ribonucleic acid

Ribonucleic acid (RNA) is a nucleic acid polymer consisting of covalently bound nucleotides. RNA nucleotides contain ribose rings and uracil unlike DNA, 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.

History
Nucleic acids were discovered in 1869 by Johann Friedrich Miescher (1844-1895), 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 uracil replaces thymine 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 (Ψ) and the DNA base thymidine are found in various places (most notably in the TΨC loop of every tRNA). 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 (there is a hydroxyl group attached to the pentose ring in the 2' position whereas DNA has a hydrogen atom rather than a hydroxyl group). This hydroxyl group makes RNA less stable than DNA because it is more prone to hydrolysis. Several types of RNA (tRNA, rRNA) contain a great deal of secondary structure, which help promote stability.

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 (usually found "upstream" of a gene). 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.

Messenger RNA (mRNA)
Main article: 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 (in eukaryotes mRNA is "processed" before being exported), 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 RNases.

Transfer RNA (tRNA)
Main article: 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 (rRNA)
Main article: Ribosomal RNA

Ribosomal RNA (rRNA) 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"
Main article: Non-coding RNA

RNA genes (sometimes referred to as non-coding RNA or small RNA) are genes that encode RNA that is not translated into a protein. The most prominent examples of RNA genes are transfer RNA (tRNA) and ribosomal RNA (rRNA), 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 (and possibly others). 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 (from Caenorhabditis elegans to Homo sapiens) and clearly plays an important role in regulating other genes.

Double-stranded RNA
Double-stranded RNA (or dsRNA) 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 may play a role in the process of RNA interference and in microRNAs.

RNA world hypothesis
The RNA world hypothesis proposes that the earliest forms of life relied on RNA both to carry genetic information (like DNA does now) and to catalyze biochemical reactions like an enzyme. According to this hypothesis, descendents of these early lifeforms gradually integrated DNA and proteins.

RNA secondary structures
Single stranded RNA molecules tend to form hydrogen bonds with itself in order to reach the minimum energy state. This leads to several recognizable "domains" of tertiary structure like hairpin loops, bulges and internal loops. Tertiary structure of RNA molecule can be predicted computationally by calculating free energies for different combinations of hydrogen bondings and domains. Online tool for structure prediction MFOLD.