Email this to a friend

A hairpin loop from a pre-mRNA. Notice its nitrogen-rich (blue) bases and oxygen-rich (red) backbone.

RNA is transcribed from DNA by enzymes called RNA polymerases and is generally further processed by other enzymes. RNA is central to the synthesis of proteins. Here, a type of RNA called messenger RNA carries information from DNA to structures called ribosomes. These ribosomes are made from proteins and ribosomal RNAs, which come together to form a molecular machine that can read messenger RNAs and translate the information they carry into proteins. There are also many RNAs involved in modifying other RNAs; some of it causing maturation of RNAs, other resulting in altered expression or products of genes.

Structure

Watson-Crick base pairs in a siRNA (hydrogen atoms are not shown)

Chemical structure of RNA

RNA is transcribed with only four bases (adenine, cytosine, guanine and uracil),^[6] but there are numerous modified bases and sugars in mature RNAs. Pseudouridine (?), in which the linkage between uracil and ribose is changed from a C?N bond to a C?C bond, and ribothymidine (T), are found in various places (most notably in the T?C loop of tRNA).^[7] Another notable modified base is hypoxanthine, a deaminated adenine base whose nucleoside is called inosine. Inosine plays a key role in the wobble hypothesis of the genetic code.^[8] There are nearly 100 other naturally occurring modified nucleosides,^[9] of which pseudouridine and nucleosides with 2'-O-methylribose are the most common.^[10] The specific roles of many of these modifications in RNA are not fully understood. However, it is notable that in ribosomal RNA, many of the post-transcriptional modifications occur in highly functional regions, such as the peptidyl transferase center and the subunit interface, implying that they are important for normal function.^[11]

Secondary structure of a telomerase RNA

Comparison with DNA

RNA and DNA differ in three main ways. First, unlike DNA which is double-stranded, RNA is a single-stranded molecule in most of its biological roles and has a much shorter chain of nucleotides. Second, while DNA contains deoxyribose, RNA contains ribose, (there is no hydroxyl group attached to the pentose ring in the 2' position in DNA). These hydroxyl groups make RNA less stable than DNA because it is more prone to hydrolysis. Third, the complementary nucleotide to adenine is not thymine, as it is in DNA, but rather uracil, which is an unmethylated form of thymine.^[14]

The 50S ribosomal subunit. RNA is in orange, protein in blue. The active site is in the middle (red).

Synthesis

Synthesis of RNA is usually catalyzed by an enzyme—RNA polymerase—using DNA as a template, a process known as transcription. Initiation of transcription 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? to 5? direction, synthesizing a complementary RNA molecule with elongation occurring in the 5? to 3? direction. The DNA sequence also dictates where termination of RNA synthesis will occur.^[17]

RNAs are often modified by enzymes after transcription. For example, a poly(A) tail and a 5' cap are added to eukaryotic pre-mRNA.

There are also a number of RNA-dependent RNA polymerases as well that use RNA as their template for synthesis of a new strand of RNA. For instance, a number of RNA viruses (such as poliovirus) use this type of enzyme to replicate their genetic material.^[18] Also, it is known that RNA-dependent RNA polymerases are required for the RNA interference pathway in many organisms.^[19]

Types of RNA

Overview

Structure of a hammerhead ribozyme, a ribozyme that cuts RNA

In translation

Messenger RNA (mRNA) carries information about a protein sequence to the ribosomes, the protein synthesis factories in the cell. It is coded so that every three nucleotides (a codon) correspond to one amino acid. In eukaryotic cells, once precursor mRNA (pre-mRNA) has been transcribed from DNA, it is processed to mature mRNA. This removes its introns—non-coding sections of the pre-mRNA. The mRNA is then exported from the nucleus to the cytoplasm, where it is bound to ribosomes and translated into its corresponding protein form with the help of tRNA. In prokaryotic cells, which do not have nucleus and cytoplasm compartments, mRNA can bind to ribosomes while it is being transcribed from DNA. After a certain amount of time the message degrades into its component nucleotides with the assistance of ribonucleases.^[20]

Transfer RNA (tRNA) is a small RNA chain of about 80 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.^[21]

Ribosomal RNA (rRNA) is the catalytic component of the ribosomes. 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. In the cytoplasm, ribosomal RNA and protein combine to form a nucleoprotein called a ribosome. The ribosome binds mRNA and carries out protein synthesis. Several ribosomes may be attached to a single mRNA at any time.^[20] rRNA is extremely abundant and makes up 80% of the 10 mg/ml RNA found in a typical eukaryotic cytoplasm.^[23]

Transfer-messenger RNA (tmRNA) is found in many bacteria and plastids. It tags proteins encoded by mRNAs that lack stop codons for degradation and prevents the ribosome from stalling.^[24]

Regulatory RNAs

Several types of RNA can downregulate gene expression by being complementary to a part of an mRNA or gene. MicroRNAs (miRNA; 21-22 nt) are found in eukaryotes and act through RNA interference (RNAi), where an effector complex of miRNA and enzymes can break down mRNA which the miRNA is complementary to, block the mRNA from being translated, or accelerate its degradation.^[25][26] While small interfering RNAs (siRNA; 20-25 nt) are often produced by breakdown of viral RNA, there are also endogenous sources of siRNAs in plants.^[27] siRNAs act through RNA interference in a fashion similar to miRNAs. Some miRNAs and siRNAs upregulate genes instead (RNA activation).^[28][29] Animals have Piwi-interacting RNAs (piRNA; 29-30 nt) which are active in germline cells and are thought to be a defense against transposons and play a role in gametogenesis.^[30][31] Antisense RNAs are widespread among bacteria; most downregulate a gene, but a few are activators of transcription.^[32] Antisense RNA can act by binding to an mRNA, forming double-stranded RNA that is degraded by enzymes.^[33] There are many mRNA-like large non-coding RNAs that regulate genes in eukaryotes,^[34] one such RNA is Xist which coats one X chromosome in female mammals and inactivates it.^[35]

An mRNA may contain regulatory elements itself, such as riboswitches, in the 5' UTR or 3' UTR; these cis-regulatory elements regulate the activity of that mRNA.^[36]

In RNA processing

Uridine to pseudouridine is a common RNA modification.

RNA genomes

Like DNA, RNA can carry genetic information. RNA viruses have genomes composed of RNA, plus a variety of proteins encoded by that genome. The viral genome is replicated by some of those proteins, while other proteins protect the genome as the virus particle moves to a new host cell. Viroids are another group of pathogens, but they consist only of RNA, do not encode any protein and are replicated by a host plant cell's polymerase.^[40]

In reverse transcription

Reverse transcribing viruses replicate their genomes by reverse transcribing DNA copies from their RNA; these DNA copies are then transcribed to new RNA. Retrotransposons also spread by copying DNA and RNA from one another,^[41] and telomerase contains an RNA that is used as template for building the ends of eukaryotic chromosomes.^[42]

Double-stranded RNA

Double-stranded RNA (dsRNA) is RNA with two complementary strands, similar to the DNA found in all cells. dsRNA forms the genetic material of some viruses (double-stranded RNA viruses). Double-stranded RNA such as viral RNA or siRNA can trigger RNA interference in eukaryotes, as well as interferon response in vertebrates.^[43][44][45]

Discovery

Nucleic acids were discovered in 1868 by Friedrich Miescher, who called the material 'nuclein' since it was found in the nucleus.^[46] It was later discovered that prokaryotic cells, which do not have a nucleus, also contain nucleic acids. The role of RNA in protein synthesis was suspected already in 1939.^[47] Severo Ochoa won the 1959 Nobel Prize in Medicine after he discovered how RNA is synthesized.^[48] The sequence of the 77 nucleotides of a yeast tRNA was found by Robert W. Holley in 1965,^[49] winning Holley the 1968 Nobel Prize in Medicine. Carl Woese realised RNA can be catalytic in 1967 and proposed that the earliest forms of life relied on RNA both to carry genetic information and to catalyze biochemical reactions—an RNA world.^[50][51] In 1976, Walter Fiers and his team determined the first complete nucleotide sequence of an RNA virus genome, that of bacteriophage MS2.^[52] In 1990 it was found that introduced genes can silence homologous endogenous genes in plants,^[53] now known to be a result of RNA interference.^[54] At about the same time, 22 nt long RNAs, now called microRNAs, were found to have a role in the development of C. elegans.^[55] The discovery of gene regulatory RNAs has led to attempts to develop drugs made of RNA, like siRNA, to silence genes.^[56]

See also

• Genetics
• Molecular biology
• Phosphoramidite
• Quantification of nucleic acids
• RNA Ontology Consortium
• Sequence profiling tool
• RNA extraction
• RNA structure prediction

References

External links

• RNA World website Link collection (structures, sequences, tools, journals)
• Nucleic Acid Database Images of DNA, RNA and complexes.

ar:??? ???? ???? bn:????? zh-min-nan:RNA bs:Ribonukleinska kiselina br:Trenkenn ribonukleek bg:??? ca:Àcid ribonucleic cs:RNA da:RNA de:Ribonukleinsäure et:Ribonukleiinhape el:RNA es:Ácido ribonucleico eo:RNA eu:Azido erribonukleiko fo:RNA fr:Acide ribonucléique gl:Ácido ribonucleico ko:RNA hr:Ribonukleinska kiselina id:Asam ribonukleat is:Ríbósakjarnsýra it:RNA he:RNA ka:????????????? ????? la:Acidum ribonucleicum lv:Ribonukle?nsk?be lb:RNS lt:Ribonukleino r?g?tis hu:Ribonukleinsav mk:??? mn:??? nl:RNA ja:???? no:RNA nn:Ribonukleinsyre oc:Acid ribonucleïc pl:Kwasy rybonukleinowe pt:Ácido ribonucleico ro:ARN ru:??????????????? ??????? sq:ARN simple:RNA sk:Ribonukleová kyselina sl:Ribonukleinska kislina sr:?????????????? ???????? sh:Ribonukleinska kiselina fi:RNA sv:Ribonukleinsyra ta:???? ??? ?????? te:???? ??????? ????? th:?????????? vi:RNA tr:RNA uk:??? ur:????? ????? ???? yo:RNA zh:????