View source for RNA

{{short description|Family of large biological molecules}}
{{about|the biological  macromolecule}}
{{pp-move}}
{{good article}}
[[File:Pre-mRNA-1ysv-tubes.png|thumb|A hairpin loop from a pre-mRNA. Highlighted are the [[nucleobase]]s (green) and the ribose-phosphate backbone (blue). This is a single strand of RNA that folds back upon itself. ]]
{{Genetics sidebar}}
'''Ribonucleic acid''' ('''RNA''') is a [[polymer]]ic molecule that is essential for most biological functions, either by performing the function itself ([[non-coding RNA]]) or by forming a template for the production of proteins ([[messenger RNA]]). RNA and [[deoxyribonucleic acid]] (DNA) are [[nucleic acid]]s. The nucleic acids constitute one of the four major [[macromolecule]]s essential for all known forms of [[life]]. RNA is assembled as a chain of [[nucleotide]]s. Cellular organisms use [[messenger RNA]] ('''''mRNA''''') to convey genetic information (using the [[nucleobase|nitrogenous bases]] of [[guanine]], [[uracil]], [[adenine]], and [[cytosine]], denoted by the letters G, U, A, and C) that directs synthesis of specific proteins. Many [[virus]]es encode their genetic information using an RNA [[genome]].
Some RNA molecules play an active role within cells by catalyzing biological reactions, controlling [[gene expression]], or sensing and communicating responses to cellular signals. One of these active processes is [[Protein biosynthesis|protein synthesis]], a universal function in which RNA molecules direct the synthesis of proteins on [[ribosome]]s. This process uses [[transfer RNA]] ('''''tRNA''''') molecules to deliver [[amino acid]]s to the [[ribosome]], where [[ribosomal RNA]] ('''''rRNA''''') then links amino acids together to form coded proteins.
It has become widely accepted in science<ref>{{cite journal | vauthors = Copley SD, Smith E, Markowitz HJ | title = The origin of the RNA world: co-evolution of genes and metabolism | journal = Bioorganic Chemistry | volume = 35 | issue = 6 | pages = 430–443 | date = December 2007 | pmid = 17897696 | doi = 10.1016/j.bioorg.2007.08.001 | quote = The proposal that life on Earth arose from an RNA World is widely accepted. }}</ref> that early in the [[history of life on Earth]], prior to the evolution of DNA and possibly of protein-based [[enzyme]]s as well, an "[[RNA world]]" existed in which RNA served as both living organisms' storage method for [[genetic information]]—a role fulfilled today by DNA, except in the case of [[RNA virus]]es—and potentially performed catalytic functions in cells—a function performed today by protein enzymes, with the notable and important exception of the ribosome, which is a [[ribozyme]].
== Chemical structure of RNA==
{{main|Nucleic acid structure}}
===Basic chemical composition===
[[File:Piwi-siRNA-basepairing.png|thumb|upright=1.15|Watson-Crick base pairs in a [[siRNA]]. Hydrogen atoms are not shown.]]
Each [[nucleotide]] in RNA contains a [[ribose]] sugar, with carbons numbered 1' through 5'. A base is attached to the 1' position, in general, [[adenine]] (A), [[cytosine]] (C), [[guanine]] (G), or [[uracil]] (U). Adenine and guanine are [[purine]]s, and cytosine and uracil are [[pyrimidine]]s. A [[phosphate]] group is attached to the 3' position of one ribose and the 5' position of the next. The phosphate groups have a negative charge each, making RNA a charged molecule (polyanion). The bases form [[hydrogen bond]]s between cytosine and guanine, between adenine and uracil and between guanine and uracil.<ref name="pmid15561141"/> However, other interactions are possible, such as a group of adenine bases binding to each other in a bulge,<ref>{{cite book|title=RNA biochemistry and biotechnology| vauthors= Barciszewski J, Frederic B, Clark C | date = 1999 | pages = 73–87 | publisher = Springer | isbn = 978-0-7923-5862-6 | oclc = 52403776 }}</ref>
or the GNRA [[tetraloop]] that has a guanine–adenine base-pair.<ref name="pmid15561141">{{cite journal |vauthors=Lee JC, Gutell RR | title = Diversity of base-pair conformations and their occurrence in rRNA structure and RNA structural motifs | journal = Journal of Molecular Biology | volume = 344 | issue = 5 | pages = 1225–49 | date = December 2004 | pmid = 15561141 | doi = 10.1016/j.jmb.2004.09.072 }}</ref>
===Differences between DNA and RNA===
[[File:50S-subunit of the ribosome 3CC2.png|thumb|Three-dimensional representation of the [[50S]] ribosomal subunit. Ribosomal RNA is in brown, proteins in blue. The active site is a small segment of rRNA, indicated in red.]]
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The chemical structure of RNA is very similar to that of [[DNA]], but differs in three primary ways:
* Unlike double-stranded DNA, RNA is usually a single-stranded molecule (ssRNA)<ref name="University of Utah-2015">{{cite web | url=https://learn.genetics.utah.edu/content/basics/rna/ | title =RNA: The Versatile Molecule | publisher =[[University of Utah]] | year =2015}}</ref> in many of its biological roles and consists of much shorter chains of nucleotides.<ref>{{cite web | url=http://www.chem.ucla.edu/harding/notes/notes_14C_nucacids.pdf | title=Nucleotides and Nucleic Acids | publisher=[[University of California, Los Angeles]] | access-date=2015-08-26 | archive-url=https://web.archive.org/web/20150923202511/http://www.chem.ucla.edu/harding/notes/notes_14C_nucacids.pdf | archive-date=2015-09-23 | url-status=dead }}</ref> However, [[RNA#Double-stranded RNA|double-stranded RNA]] (dsRNA) can form and (moreover) a single RNA molecule can, by complementary base pairing, form intrastrand double helixes, as in [[Transfer RNA|tRNA]].
* While the sugar-phosphate "backbone" of DNA contains ''[[deoxyribose]]'', RNA contains ''[[ribose]]'' instead.<ref>{{cite book | url =https://books.google.com/books?id=7-UKCgAAQBAJ&q=dna+contains+deoxyribose+rna+ribose&pg=PT386 | title =Analysis of Chromosomes | vauthors =Shukla RN | isbn =978-93-84568-17-7 | date =2014 | publisher =Agrotech Press }}{{Dead link|date=February 2023 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> Ribose has a [[Hydroxy group|hydroxyl]] group attached to the pentose ring in the [[nucleic acid nomenclature|2']] position, whereas deoxyribose does not. The hydroxyl groups in the ribose backbone make RNA more chemically [[Lability|labile]] than DNA by lowering the [[activation energy]] of [[hydrolysis]].
* The complementary base to [[adenine]] in DNA is [[thymine]], whereas in RNA, it is [[uracil]], which is an [[methylation|unmethylated]] form of thymine.<ref name=Biochemistry/>
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Like DNA, most biologically active RNAs, including [[mRNA]], [[tRNA]], [[rRNA]], [[snRNA]]s, and other [[non-coding RNA]]s, contain self-complementary sequences that allow parts of the RNA to fold<ref>{{cite journal | vauthors = Tinoco I, Bustamante C | title = How RNA folds | journal = Journal of Molecular Biology | volume = 293 | issue = 2 | pages = 271–81 | date = October 1999 | pmid = 10550208 | doi = 10.1006/jmbi.1999.3001 }}</ref> and pair with itself to form double helices. Analysis of these RNAs has revealed that they are highly structured. Unlike DNA, their structures do not consist of long double helices, but rather collections of short helices packed together into structures akin to proteins.
In this fashion, RNAs can achieve chemical [[catalysis]] (like enzymes).<ref>{{cite journal | vauthors = Higgs PG | title = RNA secondary structure: physical and computational aspects | journal = Quarterly Reviews of Biophysics | volume = 33 | issue = 3 | pages = 199–253 | date = August 2000 | pmid = 11191843 | doi = 10.1017/S0033583500003620 | s2cid = 37230785 }}</ref> For instance, determination of the structure of the ribosome—an [[Ribonucleoprotein|RNA-protein complex]] that catalyzes the assembly of proteins—revealed that its active site is composed entirely of RNA.<ref name=ribosome_activity>{{cite journal | vauthors = Nissen P, Hansen J, Ban N, Moore PB, Steitz TA | title = The structural basis of ribosome activity in peptide bond synthesis | journal = Science | volume = 289 | issue = 5481 | pages = 920–30 | date = August 2000 | pmid = 10937990 | doi = 10.1126/science.289.5481.920 | bibcode = 2000Sci...289..920N }}</ref>
[[File:RNA chemical structure.GIF|thumb|left|Structure of a fragment of an RNA, showing a guanosyl subunit]]
An important structural component of RNA that distinguishes it from DNA is the presence of a [[hydroxyl]] group at the 2' position of the [[Ribose|ribose sugar]]. The presence of this functional group causes the helix to mostly take the [[A-DNA|A-form geometry]],<ref>{{cite journal |vauthors=Salazar M, Fedoroff OY, Miller JM, Ribeiro NS, Reid BR | title = The DNA strand in DNA.RNA hybrid duplexes is neither B-form nor A-form in solution | journal = Biochemistry | volume = 32 | issue = 16 | pages = 4207–15 | date = April 1993 | pmid = 7682844 | doi = 10.1021/bi00067a007 }}</ref> although in single strand dinucleotide contexts, RNA can rarely also adopt the B-form most commonly observed in DNA.<ref>{{cite journal | vauthors = Sedova A, Banavali NK | title = RNA approaches the B-form in stacked single strand dinucleotide contexts | journal = Biopolymers | volume = 105 | issue = 2 | pages = 65–82 | date = February 2016 | pmid = 26443416 | doi = 10.1002/bip.22750 | s2cid = 35949700 }}</ref>  The A-form geometry results in a very deep and narrow major groove and a shallow and wide minor groove.<ref>{{cite journal | vauthors = Hermann T, Patel DJ | title = RNA bulges as architectural and recognition motifs | journal = Structure | volume = 8 | issue = 3 | pages = R47–54 | date = March 2000 | pmid = 10745015 | doi = 10.1016/S0969-2126(00)00110-6 | doi-access = free }}</ref> A second consequence of the presence of the 2'-hydroxyl group is that in conformationally flexible regions of an RNA molecule (that is, not involved in formation of a double helix), it can chemically attack the adjacent phosphodiester bond to cleave the backbone.<ref>{{cite journal | vauthors = Mikkola S, Stenman E, Nurmi K, Yousefi-Salakdeh E, Strömberg R, Lönnberg H | title = The mechanism of the metal ion promoted cleavage of RNA phosphodiester bonds involves a general acid catalysis by the metal aquo ion on the departure of the leaving group|journal=Journal of the Chemical Society, Perkin Transactions 2|date=1999|pages=1619–26|doi=10.1039/a903691a|issue=8}}</ref>
===Secondary and tertiary structures===
The functional form of single-stranded RNA molecules, just like proteins, frequently requires a specific spatial [[RNA Tertiary Structure|tertiary structure]]. The scaffold for this structure is provided by [[secondary structure|secondary structural]] elements that are hydrogen bonds within the molecule. This leads to several recognizable "domains" of secondary structure like [[hairpin loop]]s, bulges, and [[internal loop]]s.<ref>{{cite journal | vauthors = Mathews DH, Disney MD, Childs JL, Schroeder SJ, Zuker M, Turner DH | title = Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 19 | pages = 7287–92 | date = May 2004 | pmid = 15123812 | pmc = 409911 | doi = 10.1073/pnas.0401799101 | bibcode = 2004PNAS..101.7287M | doi-access = free }}</ref> In order to create, i.e., design, RNA for any given secondary structure, two or three bases would not be enough, but four bases are enough.<ref>{{cite journal | vauthors = Burghardt B, Hartmann AK |
title = RNA secondary structure design | journal = Physical Review E | volume = 75 | issue = 2 | pages = 021920 | date = February 2007 | doi = 10.1103/PhysRevE.75.021920 |
pmid = 17358380 | url = https://link.aps.org/doi/10.1103/PhysRevE.75.021920| arxiv = physics/0609135 |
bibcode = 2007PhRvE..75b1920B |
s2cid = 17574854 }}</ref> This is likely why nature has "chosen" a four base alphabet: fewer than four would not allow the creation of all structures, while more than four bases are not necessary to do so. Since RNA is charged, metal ions such as [[Magnesium|Mg<sup>2+</sup>]] are needed to stabilise many secondary and [[RNA Tertiary Structure|tertiary structures]].<ref>{{cite journal | vauthors = Tan ZJ, Chen SJ | title = Salt dependence of nucleic acid hairpin stability | journal = Biophysical Journal | volume = 95 | issue = 2 | pages = 738–52 | date = July 2008 | pmid = 18424500 | pmc = 2440479 | doi = 10.1529/biophysj.108.131524 | bibcode = 2008BpJ....95..738T }}</ref>
The naturally occurring [[enantiomer]] of RNA is <small>D</small>-RNA composed of <small>D</small>-ribonucleotides. All chirality centers are located in the <small>D</small>-ribose. By the use of <small>L</small>-ribose or rather <small>L</small>-ribonucleotides, <small>L</small>-RNA can be synthesized. <small>L</small>-RNA is much more stable against degradation by [[ribonuclease|RNase]].<ref name="pmid25236655">{{cite journal | vauthors = Vater A, Klussmann S | title = Turning mirror-image oligonucleotides into drugs: the evolution of Spiegelmer(®) therapeutics | journal = Drug Discovery Today | volume = 20 | issue = 1 | pages = 147–55 | date = January 2015 | pmid = 25236655 | doi = 10.1016/j.drudis.2014.09.004 | doi-access = free }}</ref>
Like other structured [[biopolymer]]s such as proteins, one can define topology of a folded RNA molecule. This is often done based on arrangement of intra-chain contacts within a folded RNA, termed as [[circuit topology]].
===Chemical modifications===
[[File:Ciliate telomerase RNA.JPG|thumb|upright=1.25|[[Secondary structure]] of a [[telomerase RNA]]]]
RNA is transcribed with only four bases (adenine, cytosine, guanine and uracil),<ref>{{cite book|title=Clinical gene analysis and manipulation: Tools, techniques and troubleshooting|vauthors=Jankowski JA, Polak JM|date=1996|page=[https://archive.org/details/clinicalgeneanal0000unse/page/14 14]|publisher=Cambridge University Press|isbn=978-0-521-47896-0|oclc=33838261|url=https://archive.org/details/clinicalgeneanal0000unse/page/14}}</ref> but these bases and attached sugars can be modified in numerous ways as the RNAs mature. [[Pseudouridine]] (Ψ), in which the linkage between uracil and ribose is changed from a C–N bond to a C–C bond, and [[5-methyluridine|ribothymidine]] (T) are found in various places (the most notable ones being in the TΨC loop of [[tRNA]]).<ref>{{cite journal | vauthors = Yu Q, Morrow CD | title = Identification of critical elements in the tRNA acceptor stem and T(Psi)C loop necessary for human immunodeficiency virus type 1 infectivity | journal = Journal of Virology | volume = 75 | issue = 10 | pages = 4902–6 | date = May 2001 | pmid = 11312362 | pmc = 114245 | doi = 10.1128/JVI.75.10.4902-4906.2001 }}</ref> Another notable modified base is [[hypoxanthine]], a deaminated adenine base whose [[nucleoside]] is called [[inosine]] (I). Inosine plays a key role in the [[wobble hypothesis]] of the [[genetic code]].<ref>{{cite journal | vauthors = Elliott MS, Trewyn RW | title = Inosine biosynthesis in transfer RNA by an enzymatic insertion of hypoxanthine | journal = The Journal of Biological Chemistry | volume = 259 | issue = 4 | pages = 2407–10 | date = February 1984 | doi = 10.1016/S0021-9258(17)43367-9 | pmid = 6365911 | doi-access = free }}</ref>
There are more than 100 other naturally occurring modified nucleosides.<ref>{{cite journal | vauthors = Cantara WA, Crain PF, Rozenski J, McCloskey JA, Harris KA, Zhang X, Vendeix FA, Fabris D, Agris PF | title = The RNA Modification Database, RNAMDB: 2011 update | journal = Nucleic Acids Research | volume = 39 | issue = Database issue | pages = D195-201 | date = January 2011 | pmid = 21071406 | pmc = 3013656 | doi = 10.1093/nar/gkq1028 }}</ref> The greatest structural diversity of modifications can be found in [[tRNA]],<ref>{{cite book|title=TRNA: Structure, biosynthesis, and function| vauthors = Söll D, RajBhandary U |date=1995|page=165|publisher=ASM Press|isbn=978-1-55581-073-3|oclc=183036381 }}</ref> while pseudouridine and nucleosides with [[2'-O-methylation|2'-O-methylribose]] often present in rRNA are the most common.<ref>{{cite journal | vauthors = Kiss T | title = Small nucleolar RNA-guided post-transcriptional modification of cellular RNAs | journal = The EMBO Journal | volume = 20 | issue = 14 | pages = 3617–22 | date = July 2001 | pmid = 11447102 | pmc = 125535 | doi = 10.1093/emboj/20.14.3617 }}</ref> 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<ref>{{cite journal | vauthors = Tirumalai MR, Rivas M, Tran Q, Fox GE | title = The Peptidyl Transferase Center: a Window to the Past. | journal = Microbiol Mol Biol Rev | volume = 85 | issue = 4 | pages = e0010421 | date = November 2021 | pmid = 34756086 | doi = 10.1128/MMBR.00104-21 | pmc = 8579967 | bibcode = 2021MMBR...85...21T }}</ref> and the subunit interface, implying that they are important for normal function.<ref>{{cite journal | vauthors = King TH, Liu B, McCully RR, Fournier MJ | title = Ribosome structure and activity are altered in cells lacking snoRNPs that form pseudouridines in the peptidyl transferase center | journal = Molecular Cell | volume = 11 | issue = 2 | pages = 425–35 | date = February 2003 | pmid = 12620230 | doi = 10.1016/S1097-2765(03)00040-6 | doi-access = free }}</ref>
==Types of RNA==
{{see also|List of RNAs}}
[[File:Full length hammerhead ribozyme.png|thumb|upright|Structure of a [[hammerhead ribozyme]], a ribozyme that cuts RNA]]
Messenger RNA (mRNA) is the type of RNA that carries information from DNA to the [[ribosome]], the sites of protein synthesis ([[Translation (biology)|translation]]) in the cell cytoplasm. The coding sequence of the mRNA determines the [[amino acid]] sequence in the [[protein]] that is produced.<ref name=The_Cell/> However, many RNAs do not code for protein (about 97% of the transcriptional output is non-protein-coding in eukaryotes<ref>{{cite journal | vauthors = Mattick JS, Gagen MJ | title = The evolution of controlled multitasked gene networks: the role of introns and other noncoding RNAs in the development of complex organisms | journal = Molecular Biology and Evolution | volume = 18 | issue = 9 | pages = 1611–30 | date = September 2001 | pmid = 11504843 | doi = 10.1093/oxfordjournals.molbev.a003951 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Mattick JS | title = Non-coding RNAs: the architects of eukaryotic complexity | journal = EMBO Reports | volume = 2 | issue = 11 | pages = 986–91 | date = November 2001 | pmid = 11713189 | pmc = 1084129 | doi = 10.1093/embo-reports/kve230 }}</ref><ref>{{cite journal | vauthors = Mattick JS | title = Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms | journal = BioEssays | volume = 25 | issue = 10 | pages = 930–39 | date = October 2003 | pmid = 14505360 | doi = 10.1002/bies.10332 | url = http://www.imb-jena.de/jcb/journal_club/mattick2003.pdf | citeseerx = 10.1.1.476.7561 | archive-url = https://web.archive.org/web/20090306105646/http://www.imb-jena.de/jcb/journal_club/mattick2003.pdf | url-status=dead | archive-date = 2009-03-06 }}</ref><ref>{{cite journal | vauthors = Mattick JS | title = The hidden genetic program of complex organisms | journal = Scientific American | volume = 291 | issue = 4 | pages = 60–67 | date = October 2004 | pmid = 15487671 | doi = 10.1038/scientificamerican1004-60 | bibcode = 2004SciAm.291d..60M }}{{dead link|date=June 2016|bot=medic}}{{cbignore|bot=medic}}</ref>).
These so-called [[non-coding RNA]]s ("ncRNA") can be encoded by their own genes (RNA genes), but can also derive from mRNA [[intron]]s.<ref name=transcriptome/> The most prominent examples of non-coding RNAs are [[transfer RNA]] (tRNA) and [[ribosomal RNA]] (rRNA), both of which are involved in the process of translation.<ref name=Biochemistry>{{cite book | vauthors = Berg JM, Tymoczko JL, Stryer L |title= Biochemistry|edition=5th|pages =118–19, 781–808|publisher= WH Freeman and Company|date=2002|isbn= 978-0-7167-4684-3|oclc=179705944 }}</ref> There are also non-coding RNAs involved in gene regulation, [[RNA processing]] and other roles. Certain RNAs are able to [[catalysis|catalyse]] chemical reactions such as cutting and [[ligase|ligating]] other RNA molecules,<ref>{{cite journal | vauthors = Rossi JJ | title = Ribozyme diagnostics comes of age | journal = Chemistry & Biology | volume = 11 | issue = 7 | pages = 894–95 | date = July 2004 | pmid = 15271347 | doi = 10.1016/j.chembiol.2004.07.002 | doi-access = free }}</ref> and the catalysis of [[peptide bond]] formation in the [[ribosome]];<ref name=ribosome_activity/> these are known as [[ribozyme]]s.
According to the length of RNA chain, RNA includes [[small RNA]] and long RNA.<ref name="Noncoding RNA">{{cite journal | vauthors = Storz G | title = An expanding universe of noncoding RNAs | journal = Science | volume = 296 | issue = 5571 | pages = 1260–63 | date = May 2002 | pmid = 12016301 | doi = 10.1126/science.1072249 | bibcode = 2002Sci...296.1260S | s2cid = 35295924 }}</ref> Usually, [[small RNA]]s are shorter than 200&nbsp;[[Nucleotide|nt]] in length, and long RNAs are greater than 200&nbsp;[[Nucleotide|nt]] long.<ref name="lncRNA">{{cite journal | vauthors = Fatica A, Bozzoni I | title = Long non-coding RNAs: new players in cell differentiation and development | journal = Nature Reviews Genetics | volume = 15 | issue = 1 | pages = 7–21 | date = January 2014 | pmid = 24296535 | doi = 10.1038/nrg3606 | s2cid = 12295847 | url = https://hal-riip.archives-ouvertes.fr/pasteur-01160208/document }}{{Dead link|date=November 2018 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> Long RNAs, also called large RNAs, mainly include [[long non-coding RNA]] (lncRNA) and [[mRNA]]. Small RNAs mainly include 5.8S [[ribosomal RNA]] (rRNA), [[5S rRNA]], [[transfer RNA]] (tRNA), [[microRNA]] (miRNA), [[small interfering RNA]] (siRNA), [[small nucleolar RNA]] (snoRNAs), [[Piwi-interacting RNA]] (piRNA), tRNA-derived small RNA (tsRNA)<ref name="tsRNA">{{cite journal | vauthors = Chen Q, Yan M, Cao Z, Li X, Zhang Y, Shi J, Feng GH, Peng H, Zhang X, Zhang Y, Qian J, Duan E, Zhai Q, Zhou Q  | display-authors = 6 | title = Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder | journal = Science | volume = 351 | issue = 6271 | pages = 397–400 | date = January 2016 | pmid = 26721680 | doi = 10.1126/science.aad7977 | bibcode = 2016Sci...351..397C | s2cid = 21738301 | url = https://escholarship.org/content/qt6x66v4k6/qt6x66v4k6.pdf?t=plrd95 }}</ref> and small rDNA-derived RNA (srRNA).<ref name="srRNA">{{cite journal | vauthors = Wei H, Zhou B, Zhang F, Tu Y, Hu Y, Zhang B, Zhai Q | title = Profiling and identification of small rDNA-derived RNAs and their potential biological functions | journal = PLOS ONE | volume = 8 | issue = 2 | pages = e56842 | date = 2013 | pmid = 23418607 | pmc = 3572043 | doi = 10.1371/journal.pone.0056842 | bibcode = 2013PLoSO...856842W | doi-access = free }}</ref>
There are certain exceptions as in the case of the [[5S rRNA]] of the members of the genus [[Halococcus]] ([[Archaea]]), which have an insertion, thus increasing its size.<ref>{{cite journal | vauthors = Luehrsen KR, Nicholson DE, Eubanks DC, Fox GE | title = An archaebacterial 5S rRNA contains a long insertion sequence. | journal = Nature | year = 1981 | volume =  293| issue =  5835| pages = 755–756| pmid =  6169998| doi = 10.1038/293755a0  | bibcode = 1981Natur.293..755L | s2cid = 4341755 }}</ref><ref>{{cite journal | vauthors = Stan-Lotter H, McGenity TJ, Legat A, Denner EB, Glaser K, Stetter KO, Wanner G | title = Very similar strains of Halococcus salifodinae are found in geographically separated permo-triassic salt deposits. | journal = Microbiology | volume = 145| issue = Pt 12| pages = 3565–3574 | date = 1999| pmid = 10627054 | doi = 10.1099/00221287-145-12-3565 | doi-access = free }}</ref><ref>{{cite journal |vauthors=Tirumalai MR, Kaelber JT, Park DR, Tran Q, Fox GE |title=Cryo-Electron Microscopy Visualization of a Large Insertion in the 5S ribosomal RNA of the Extremely Halophilic Archaeon ''Halococcus morrhuae'' |journal= FEBS Open Bio|date=August 2020 |volume=10 |issue=10 |pages=1938–1946 |pmid= 32865340| doi = 10.1002/2211-5463.12962|pmc=7530397 |bibcode=2020FEBOB..10.1938T }}</ref>
===RNAs involved in protein synthesis===
[[Messenger RNA]] (mRNA) carries information about a protein sequence to the [[ribosome]]s, the protein synthesis factories in the cell. It is [[genetic code|coded]] so that every three nucleotides (a [[codon]]) corresponds 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 [[intron]]s—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 [[Translation (biology)|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 [[ribonuclease]]s.<ref name=The_Cell/>
[[Transfer RNA]] (tRNA) is a small RNA chain of about 80 [[nucleotide]]s 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.<ref name=transcriptome/>
[[File:Translation of mRNA.svg|thumb|A diagram of how mRNA is used to create polypeptide chains]]
[[Ribosomal RNA]] (rRNA) is the catalytic component of the ribosomes. The rRNA is the component of the ribosome that hosts translation. 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.<ref name=The_Cell>{{cite book|title=The Cell: A Molecular Approach|edition=3rd| vauthors = Cooper GC, Hausman RE | date = 2004|pages=261–76, 297, 339–44|publisher=Sinauer|isbn=978-0-87893-214-6|oclc=174924833 }}</ref> Nearly all the RNA found in a typical eukaryotic cell is rRNA.
[[tmRNA|Transfer-messenger RNA]] (tmRNA) is found in many [[bacteria]] and [[plastid]]s. It tags proteins encoded by mRNAs that lack stop codons for degradation and prevents the ribosome from stalling.<ref>{{cite journal | vauthors = Gueneau de Novoa P, Williams KP | title = The tmRNA website: reductive evolution of tmRNA in plastids and other endosymbionts | journal = Nucleic Acids Research | volume = 32 | issue = Database issue | pages = D104–08 | date = January 2004 | pmid = 14681369 | pmc = 308836 | doi = 10.1093/nar/gkh102 }}</ref>
=== Regulatory RNA ===
The earliest known regulators of [[gene expression]] were proteins known as [[repressor]]s and [[Activator (genetics)|activators]] – regulators with specific short binding sites within [[Enhancer (genetics)|enhancer]] regions near the genes to be regulated.<ref>{{cite journal | vauthors = Jacob F, Monod J | year = 1961 | title = Genetic Regulatory Mechanisms in the Synthesis of Proteins | journal = Journal of Molecular Biology | volume = 3 | issue = 3| pages = 318–56 | doi = 10.1016/s0022-2836(61)80072-7 | pmid = 13718526 | s2cid = 19804795 }}</ref>&nbsp; Later studies have shown that RNAs also regulate genes. There are several kinds of RNA-dependent processes in eukaryotes regulating the expression of genes at various points, such as [[RNA interference|RNAi]] repressing genes [[Post-transcriptional regulation|post-transcriptionally]],  [[long non-coding RNA]]s shutting down blocks of [[chromatin]] [[epigenetically]], and [[enhancer RNA]]s inducing increased gene expression.<ref name="Morris-2014">{{cite journal | vauthors = Morris K, Mattick J | year = 2014 | title = The rise of regulatory RNA | journal = Nature Reviews Genetics | volume = 15 | issue = 6| pages = 423–37 | doi = 10.1038/nrg3722 | pmid = 24776770 | pmc = 4314111 }}</ref> [[Prokaryote|Bacteria and archaea]]  have also been shown to use regulatory RNA systems such as [[bacterial small RNA]]s and [[CRISPR]].<ref name="Gottesman-2005">{{cite journal | vauthors = Gottesman S | year = 2005 | title = Micros for microbes: non-coding regulatory RNAs in bacteria | journal = Trends in Genetics | volume = 21 | issue = 7| pages = 399–404 | doi = 10.1016/j.tig.2005.05.008 | pmid = 15913835 }}</ref>  Fire and Mello were awarded the 2006 [[Nobel Prize in Physiology or Medicine]] for discovering [[microRNA]]s  (miRNAs), specific short RNA molecules that can base-pair with mRNAs.<ref name="Nobel Prize-2006">"The Nobel Prize in Physiology or Medicine 2006". ''Nobelprize.org.'' Nobel Media AB 2014. Web. 6 Aug 2018. http://www.nobelprize.org/nobel_prizes/medicine/laureates/2006</ref>
==== MicroRNA (miRNA) and small interfering RNA (siRNA) ====
{{See also|RNA interference}}
Post-transcriptional expression levels of many genes can be controlled by [[RNA interference]], in which [[miRNA]]s, specific short RNA molecules, pair with mRNA regions and target them for degradation.<ref>{{cite journal | vauthors = Fire  | display-authors = etal | year = 1998 | title = Potent and Specific Genetic Interference by double stranded RNA in Ceanorhabditis elegans | journal = Nature | volume = 391 | issue = 6669| pages = 806–11 | doi = 10.1038/35888 | pmid = 9486653 | bibcode = 1998Natur.391..806F | s2cid = 4355692 | url = http://www.dspace.cam.ac.uk/handle/1810/238264 }}</ref>  This [[Antisense RNA|antisense]]-based process involves steps that first process the RNA so that it can [[Base pair|base-pair]] with a region of its target mRNAs. Once the base pairing occurs, other proteins direct the mRNA to be destroyed by [[nuclease]]s.<ref name="Morris-2014" />
==== Long non-coding RNAs ====
{{See also|Long non-coding RNA|l1=Long Non-coding RNA}}
Next to be linked to regulation were [[XIST|Xist]] and other [[long noncoding RNA]]s associated with [[X chromosome inactivation]].&nbsp; Their roles, at first mysterious, were shown by [[Jeannie T. Lee]] and others to be the [[RNA silencing|silencing]] of blocks of chromatin via recruitment of [[Polycomb-group proteins|Polycomb]] complex so that messenger RNA could not be transcribed from them.<ref>{{cite journal | vauthors = Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT | year = 2008 | title = Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome | journal = Science | volume = 322 | issue = 5902| pages = 750–56 | pmid = 18974356 | doi = 10.1126/science.1163045 | pmc = 2748911 | bibcode = 2008Sci...322..750Z }}</ref> Additional lncRNAs, currently defined as RNAs of more than 200 base pairs that do not appear to have coding potential,<ref name="Rinn-2012">{{cite journal | vauthors = Rinn JL, Chang HY | year = 2012 | title = Genome regulation by long noncoding RNAs | journal = Annu. Rev. Biochem. | volume = 81 | pages = 1–25 | doi = 10.1146/annurev-biochem-051410-092902 | pmid = 22663078 | pmc = 3858397 }}</ref> have been found associated with regulation of [[stem cell]] [[pluripotency]] and [[cell division]].<ref name="Rinn-2012" />
==== Enhancer RNAs ====
{{See also|Enhancer RNA}}
The third major group of regulatory RNAs is called [[enhancer RNA]]s.<ref name="Rinn-2012" /> &nbsp;It is not clear at present whether they are a unique category of RNAs of various lengths or&nbsp;constitute a distinct subset of lncRNAs.&nbsp; In any case, they are transcribed from [[enhancers]], which are known regulatory sites in the DNA near genes they regulate.<ref name="Rinn-2012" /><ref>{{cite journal | vauthors = Taft RJ, Kaplan CD, Simons C, Mattick JS | year = 2009 | title = Evolution, biogenesis and function of promoter- associated RNAs | journal = Cell Cycle | volume = 8 | issue = 15| pages = 2332–38 | doi = 10.4161/cc.8.15.9154 | pmid = 19597344 | doi-access = free }}</ref> &nbsp;They up-regulate the transcription of the gene(s) under control of the enhancer from which they are transcribed.<ref name="Rinn-2012" /><ref>{{cite journal | vauthors = Orom UA, Derrien T, Beringer M, Gumireddy K, Gardini A | display-authors = etal | year = 2010 | title = 'Long noncoding RNAs with enhancer-like function in human cells | journal = Cell | volume = 143 | issue = 1| pages = 46–58 | pmid = 20887892 | doi = 10.1016/j.cell.2010.09.001 | pmc = 4108080 }}</ref>
=== Small RNA in prokaryotes ===
====Small RNA====
At first, regulatory RNA was thought to be a eukaryotic phenomenon, a part of the explanation for why so much more transcription in higher organisms was seen than had been predicted. But as soon as researchers began to look for possible RNA regulators in bacteria, they turned up there as well, termed as small RNA (sRNA).<ref>EGH Wagner, P Romby. (2015). "Small RNAs in bacteria and archaea: who they are, what they do, and how they do it". ''Advances in genetics'' (Vol. 90, pp. 133–208).</ref><ref name="Gottesman-2005" />  Currently, the ubiquitous nature of systems of RNA regulation of genes has been discussed as support for the [[RNA World]] theory.<ref name="Morris-2014" /><ref>J.W. Nelson, R.R. Breaker (2017) "The lost language of the RNA World."''Sci. Signal''.'''10''', eaam8812 1–11.</ref> There are indications that the enterobacterial sRNAs are involved in various cellular processes and seem to have significant role in stress responses such as membrane stress, starvation stress, phosphosugar stress and DNA damage. Also, it has been suggested that sRNAs have been evolved to have important role in stress responses because of their kinetic properties that allow for rapid response and stabilisation of the physiological state.<ref name="University of Utah-2015" /> [[Bacterial small RNA]]s generally act via [[Antisense RNA|antisense]] pairing with mRNA to down-regulate its translation, either by affecting stability or affecting cis-binding ability.<ref name="Morris-2014" /> [[Riboswitch]]es have also been discovered. They are cis-acting regulatory RNA sequences acting [[Allosteric regulation|allosterically]].  They change shape when they bind [[metabolite]]s so that they gain or lose the ability to bind chromatin to regulate expression of genes.<ref>{{cite journal | vauthors = Winklef WC | year = 2005 | title = Riboswitches and the role of noncoding RNAs in bacterial metabolic control | journal = Curr. Opin. Chem. Biol. | volume = 9 | issue = 6| pages = 594–602 | doi = 10.1016/j.cbpa.2005.09.016 | pmid = 16226486 }}</ref><ref>{{cite journal | vauthors = Tucker BJ, Breaker RR | year = 2005 | title = Riboswitches as versatile gene control elements | journal = Curr. Opin. Struct. Biol. | volume = 15 | issue = 3| pages = 342–48 | doi = 10.1016/j.sbi.2005.05.003 | pmid = 15919195 }}</ref>
====CRISPR RNA====
Archaea also have systems of regulatory RNA.<ref>{{cite journal | vauthors = Mojica FJ, Diez-Villasenor C, Soria E, Juez G | year = 2000 | title = "&nbsp;"Biological significance of a family of regularly spaced repeats in the genomes of archaea, bacteria and mitochondria | journal = Mol. Microbiol. | volume = 36 | issue = 1| pages = 244–46 | doi = 10.1046/j.1365-2958.2000.01838.x | pmid = 10760181 | s2cid = 22216574 | doi-access = free }}</ref>  The CRISPR system, recently being used to edit DNA ''in situ'', acts via regulatory RNAs in archaea and bacteria to provide protection against virus invaders.<ref name="Morris-2014" /><ref>{{cite journal | vauthors = Brouns S, Jore MM, Lundgren M, Westra E, Slijkhuis R, Snijders A, Dickman M, Makarova K, Koonin E, Der Oost JV | year = 2008 | title = Small CRISPR RNAs guide antiviral defense in prokaryotes | journal = Science | volume = 321 | issue = 5891| pages = 960–64 | doi = 10.1126/science.1159689 | pmid = 18703739 | pmc = 5898235 | bibcode = 2008Sci...321..960B }}</ref>
==RNA synthesis and processing==
===Synthesis===
Synthesis of RNA typically occurs in the cell nucleus and is usually catalyzed by an enzyme—[[RNA polymerase]]—using DNA as a template, a process known as [[Transcription (genetics)|transcription]]. Initiation of transcription begins with the binding of the enzyme to a [[promoter (biology)|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.<ref>{{cite journal | vauthors = Nudler E, Gottesman ME | title = Transcription termination and anti-termination in E. coli | journal = Genes to Cells | volume = 7 | issue = 8 | pages = 755–68 | date = August 2002 | pmid = 12167155 | doi = 10.1046/j.1365-2443.2002.00563.x | s2cid = 23191624 | doi-access =  }}</ref>
[[Primary transcript]] RNAs are often [[Post-transcriptional modification|modified]] by enzymes after transcription. For example, a [[poly(A) tail]] and a [[5' cap]] are added to eukaryotic [[pre-mRNA]] and [[intron]]s are removed by the [[spliceosome]].
There are also a number of [[RNA-dependent RNA polymerase]]s that use RNA as their template for synthesis of a new strand of RNA. For instance, a number of [[Orthornavirae|RNA viruses]] (such as poliovirus) use this type of enzyme to replicate their genetic material.<ref>{{cite journal | vauthors = Hansen JL, Long AM, Schultz SC | title = Structure of the RNA-dependent RNA polymerase of poliovirus | journal = Structure | volume = 5 | issue = 8 | pages = 1109–22 | date = August 1997 | pmid = 9309225 | doi = 10.1016/S0969-2126(97)00261-X | doi-access = free }}</ref> Also, RNA-dependent RNA polymerase is part of the [[RNA interference]] pathway in many organisms.<ref>{{cite journal | vauthors = Ahlquist P | title = RNA-dependent RNA polymerases, viruses, and RNA silencing | journal = Science | volume = 296 | issue = 5571 | pages = 1270–73 | date = May 2002 | pmid = 12016304 | doi = 10.1126/science.1069132 | bibcode = 2002Sci...296.1270A | s2cid = 42526536 }}</ref>
=== RNA processing ===
[[File:Synthesis of Pseudouridine.svg|thumb|Uridine to pseudouridine is a common RNA modification.]]
Many RNAs are involved in modifying other RNAs.
[[Intron]]s are [[Splicing (genetics)|spliced]] out of [[pre-mRNA]] by [[spliceosome]]s, which contain several [[small nuclear RNA]]s (snRNA),<ref name=Biochemistry/> or the introns can be ribozymes that are spliced by themselves.<ref>{{cite journal | vauthors = Steitz TA, Steitz JA | title = A general two-metal-ion mechanism for catalytic RNA | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 14 | pages = 6498–502 | date = July 1993 | pmid = 8341661 | pmc = 46959 | doi = 10.1073/pnas.90.14.6498 | bibcode = 1993PNAS...90.6498S | doi-access = free }}</ref>
RNA can also be altered by having its nucleotides modified to  nucleotides other than [[adenosine|A]], [[cytidine|C]], [[guanosine|G]] and [[uridine|U]].
In eukaryotes, modifications of RNA nucleotides are in general directed by [[small nucleolar RNA]]s (snoRNA; 60–300&nbsp;nt),<ref name=transcriptome>{{cite book|title=Mining the transcriptome&nbsp;– methods and applications|url=http://kth.diva-portal.org/smash/get/diva2:10803/FULLTEXT01 | vauthors = Wirta W |date=2006|isbn=978-91-7178-436-0|publisher=School of Biotechnology, Royal Institute of Technology|location=Stockholm|oclc=185406288}}</ref> found in the [[nucleolus]] and [[Cajal body|cajal bodies]]. snoRNAs associate with enzymes and guide them to a spot on an RNA by basepairing to that RNA. These enzymes then perform the nucleotide modification. rRNAs and tRNAs are extensively modified, but snRNAs and mRNAs can also be the target of base modification.<ref>{{cite journal | vauthors = Xie J, Zhang M, Zhou T, Hua X, Tang L, Wu W | title = Sno/scaRNAbase: a curated database for small nucleolar RNAs and cajal body-specific RNAs | journal = Nucleic Acids Research | volume = 35 | issue = Database issue | pages = D183–87 | date = January 2007 | pmid = 17099227 | pmc = 1669756 | doi = 10.1093/nar/gkl873 }}</ref><ref>{{cite journal | vauthors = Omer AD, Ziesche S, Decatur WA, Fournier MJ, Dennis PP | title = RNA-modifying machines in archaea | journal = Molecular Microbiology | volume = 48 | issue = 3 | pages = 617–29 | date = May 2003 | pmid = 12694609 | doi = 10.1046/j.1365-2958.2003.03483.x | s2cid = 20326977 | doi-access =  }}</ref> RNA can also be methylated.<ref>{{cite journal | vauthors = Cavaillé J, Nicoloso M, Bachellerie JP | title = Targeted ribose methylation of RNA in vivo directed by tailored antisense RNA guides | journal = Nature | volume = 383 | issue = 6602 | pages = 732–35 | date = October 1996 | pmid = 8878486 | doi = 10.1038/383732a0 | bibcode = 1996Natur.383..732C | s2cid = 4334683 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Kiss-László Z, Henry Y, Bachellerie JP, Caizergues-Ferrer M, Kiss T | title = Site-specific ribose methylation of preribosomal RNA: a novel function for small nucleolar RNAs | journal = Cell | volume = 85 | issue = 7 | pages = 1077–88 | date = June 1996 | pmid = 8674114 | doi = 10.1016/S0092-8674(00)81308-2 | s2cid = 10418885 | doi-access = free }}</ref>
==RNA in genetics==
===RNA genomes===
Like DNA, RNA can carry genetic information. [[RNA virus]]es have [[genome]]s composed of RNA that encodes a number of proteins. 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. [[Viroid]]s 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.<ref>{{cite journal | vauthors = Daròs JA, Elena SF, Flores R | title = Viroids: an Ariadne's thread into the RNA labyrinth | journal = EMBO Reports | volume = 7 | issue = 6 | pages = 593–98 | date = June 2006 | pmid = 16741503 | pmc = 1479586 | doi = 10.1038/sj.embor.7400706 }}</ref>
===Reverse transcription===
Reverse transcribing viruses replicate their genomes by [[Reverse transcription|reverse transcribing]] DNA copies from their RNA; these DNA copies are then transcribed to new RNA. [[Retrotransposon]]s also spread by copying DNA and RNA from one another,<ref>{{cite journal | vauthors = Kalendar R, Vicient CM, Peleg O, Anamthawat-Jonsson K, Bolshoy A, Schulman AH | title = Large retrotransposon derivatives: abundant, conserved but nonautonomous retroelements of barley and related genomes | journal = Genetics | volume = 166 | issue = 3 | pages = 1437–50 | date = March 2004 | pmid = 15082561 | pmc = 1470764 | doi = 10.1534/genetics.166.3.1437 }}</ref> and [[telomerase]] contains an [[Telomerase RNA component|RNA that is used as template]] for building the ends of [[Eukaryotic chromosome structure|eukaryotic chromosomes]].<ref>{{cite journal | vauthors = Podlevsky JD, Bley CJ, Omana RV, Qi X, Chen JJ | title = The telomerase database | journal = Nucleic Acids Research | volume = 36 | issue = Database issue | pages = D339–43 | date = January 2008 | pmid = 18073191 | pmc = 2238860 | doi = 10.1093/nar/gkm700 }}</ref>
=== Double-stranded RNA ===
[[File:Double-stranded RNA.gif|thumb|Double-stranded RNA]]{{Main articles|Double-stranded RNA}}
[[Double-stranded RNA]] (dsRNA) is RNA with two complementary strands, similar to the DNA found in all cells, but with the replacement of thymine by uracil and the adding of one oxygen atom. dsRNA forms the genetic material of some [[virus]]es ([[double-stranded RNA viruses]]). Double-stranded RNA, such as viral RNA or [[siRNA]], can trigger [[RNA interference]] in [[eukaryote]]s, as well as [[interferon]] response in [[vertebrate]]s.<ref>{{cite journal | vauthors = Blevins T, Rajeswaran R, Shivaprasad PV, Beknazariants D, Si-Ammour A, Park HS, Vazquez F, Robertson D, Meins F, Hohn T, Pooggin MM | title = Four plant Dicers mediate viral small RNA biogenesis and DNA virus induced silencing | journal = Nucleic Acids Research | volume = 34 | issue = 21 | pages = 6233–46 | date = 2006 | pmid = 17090584 | pmc = 1669714 | doi = 10.1093/nar/gkl886 }}
</ref><ref>{{cite journal | vauthors = Jana S, Chakraborty C, Nandi S, Deb JK | title = RNA interference: potential therapeutic targets | journal = Applied Microbiology and Biotechnology | volume = 65 | issue = 6 | pages = 649–57 | date = November 2004 | pmid = 15372214 | doi = 10.1007/s00253-004-1732-1 | s2cid = 20963666 }}</ref><ref>{{cite journal |last=Virol |first=J |date=May 2006 |title=Double-Stranded RNA Is Produced by Positive-Strand RNA Viruses and DNA Viruses but Not in Detectable Amounts by Negative-Strand RNA Viruses |journal=Journal of Virology |volume=80 |issue=10 |pages=5059–5064 |doi=10.1128/JVI.80.10.5059-5064.2006 |pmid=16641297 |pmc=1472073 }}</ref><ref>{{cite journal | vauthors = Schultz U, Kaspers B, Staeheli P | title = The interferon system of non-mammalian vertebrates | journal = Developmental and Comparative Immunology | volume = 28 | issue = 5 | pages = 499–508 | date = May 2004 | pmid = 15062646 | doi = 10.1016/j.dci.2003.09.009 }}</ref> In eukaryotes, double-stranded RNA (dsRNA) plays a role in the activation of the [[innate immune system]] against viral infections.<ref>{{cite journal | vauthors = Whitehead KA, Dahlman JE, Langer RS, Anderson DG | title = Silencing or stimulation? siRNA delivery and the immune system | journal = Annual Review of Chemical and Biomolecular Engineering | volume = 2 | pages = 77–96 | year = 2011 | pmid = 22432611 | doi = 10.1146/annurev-chembioeng-061010-114133 }}</ref>
=== Circular RNA ===
{{main|Circular RNA}}
In the late 1970s, it was shown that there is a single stranded covalently closed, i.e. circular form of RNA expressed throughout the animal and plant kingdom (see [[Circular RNA|circRNA]]).<ref>{{cite journal | vauthors = Hsu MT, Coca-Prados M | title = Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells | language = En | journal = Nature | volume = 280 | issue = 5720 | pages = 339–40 | date = July 1979 | pmid = 460409 | doi = 10.1038/280339a0 | bibcode = 1979Natur.280..339H | s2cid = 19968869 }}</ref> circRNAs are thought to arise via a "back-splice" reaction where the [[spliceosome]] joins a upstream 3' acceptor to a downstream 5' donor splice site. So far the function of circRNAs is largely unknown, although for few examples a microRNA sponging activity has been demonstrated.
==Key discoveries in RNA biology==
{{further|History of RNA biology}}
[[File:R Holley.jpg|thumb|210px|Robert W. Holley, left, poses with his research team.]]
Research on RNA has led to many important biological discoveries and numerous [[Nobel Prize]]s. [[Nucleic acid]]s were discovered in 1868 by [[Friedrich Miescher]], who called the material 'nuclein' since it was found in the [[Cell nucleus|nucleus]].<ref>{{cite journal | vauthors = Dahm R | title = Friedrich Miescher and the discovery of DNA | journal = Developmental Biology | volume = 278 | issue = 2 | pages = 274–88 | date = February 2005 | pmid = 15680349 | doi = 10.1016/j.ydbio.2004.11.028 | doi-access =  }}</ref> It was later discovered that [[Prokaryote|prokaryotic]] cells, which do not have a nucleus, also contain nucleic acids. The role of RNA in protein synthesis was suspected already in 1939.<ref>{{cite journal|journal=Nature | vauthors = Caspersson T, Schultz J | title = Pentose nucleotides in the cytoplasm of growing tissues|date=1939|volume=143|doi=10.1038/143602c0|pages=602–03|issue=3623|bibcode=1939Natur.143..602C| s2cid = 4140563 }}</ref> [[Severo Ochoa]] won the 1959 [[Nobel Prize in Medicine]] (shared with [[Arthur Kornberg]]) after he discovered an enzyme that can synthesize RNA in the laboratory.<ref>{{cite web | vauthors = Ochoa S | title = Enzymatic synthesis of ribonucleic acid|work=Nobel Lecture|date=1959|url=http://nobelprize.org/nobel_prizes/medicine/laureates/1959/ochoa-lecture.pdf}}</ref> However, the enzyme discovered by Ochoa ([[polynucleotide phosphorylase]]) was later shown to be responsible for RNA degradation, not RNA synthesis. In 1956 Alex Rich and David Davies hybridized two separate strands of RNA to form the first crystal of RNA whose structure could be determined by X-ray crystallography.<ref>{{cite journal | vauthors = Rich A, Davies D |title=A New Two-Stranded Helical Structure: Polyadenylic Acid and Polyuridylic Acid|journal=Journal of the American Chemical Society|date=1956|volume=78|issue=14|doi=10.1021/ja01595a086|pages=3548–49}}</ref>
The sequence of the 77 nucleotides of a yeast tRNA was found by [[Robert W. Holley]] in 1965,<ref>{{cite journal | vauthors = Holley RW, Apgar J, Everett GA, Madison JT, Marquisee M, Merrill SH, Penswick JR, Zamir A | title = Structure of a ribonucleic acid | journal = Science | volume = 147 | issue = 3664 | pages = 1462–65 | date = March 1965 | pmid = 14263761 | doi = 10.1126/science.147.3664.1462 | bibcode = 1965Sci...147.1462H | s2cid = 40989800 | display-authors = 1 }}</ref> winning Holley the [[List of Nobel laureates in Physiology or Medicine|1968 Nobel Prize in Medicine]] (shared with [[Har Gobind Khorana]] and [[Marshall Nirenberg]]).
In the early 1970s, [[retrovirus]]es and [[reverse transcriptase]] were discovered, showing for the first time that enzymes could copy RNA into DNA (the opposite of the usual route for transmission of genetic information). For this work, [[David Baltimore]], [[Renato Dulbecco]] and [[Howard Temin]] were awarded a Nobel Prize in 1975.
In 1976, [[Walter Fiers]] and his team determined the first complete nucleotide sequence of an RNA virus genome, that of [[bacteriophage MS2]].<ref>{{cite journal | vauthors = Fiers W, Contreras R, Duerinck F, Haegeman G, Iserentant D, Merregaert J, Min Jou W, Molemans F, Raeymaekers A, Van den Berghe A, Volckaert G, Ysebaert M | title = Complete nucleotide sequence of bacteriophage MS2 RNA: primary and secondary structure of the replicase gene | journal = Nature | volume = 260 | issue = 5551 | pages = 500–07 | date = April 1976 | pmid = 1264203 | doi = 10.1038/260500a0 | bibcode = 1976Natur.260..500F | s2cid = 4289674 | display-authors = 1 }}</ref>
In 1977, [[intron]]s and [[RNA splicing]] were discovered in both mammalian viruses and in cellular genes, resulting in a 1993 Nobel to [[Philip A. Sharp|Philip Sharp]] and [[Richard J. Roberts|Richard Roberts]].
Catalytic RNA molecules ([[ribozyme]]s) were discovered in the early 1980s, leading to a 1989 Nobel award to [[Thomas Cech]] and [[Sidney Altman]]. In 1990, it was found in ''[[Petunia]]'' that introduced genes can silence similar genes of the plant's own, now known to be a result of [[RNA interference]].<ref>{{cite journal | vauthors = Napoli C, Lemieux C, Jorgensen R | title = Introduction of a Chimeric Chalcone Synthase Gene into Petunia Results in Reversible Co-Suppression of Homologous Genes in trans | journal = The Plant Cell | volume = 2 | issue = 4 | pages = 279–89 | date = April 1990 | pmid = 12354959 | pmc = 159885 | doi = 10.1105/tpc.2.4.279 }}</ref><ref>{{cite journal | vauthors = Dafny-Yelin M, Chung SM, Frankman EL, Tzfira T | title = pSAT RNA interference vectors: a modular series for multiple gene down-regulation in plants | journal = Plant Physiology | volume = 145 | issue = 4 | pages = 1272–81 | date = December 2007 | pmid = 17766396 | pmc = 2151715 | doi = 10.1104/pp.107.106062 }}</ref>
At about the same time, 22 nt long RNAs, now called [[microRNA]]s, were found to have a role in the [[developmental biology|development]] of ''[[Caenorhabditis elegans|C. elegans]]''.<ref>{{cite journal | vauthors = Ruvkun G | s2cid = 83506718 | title = Molecular biology. Glimpses of a tiny RNA world | journal = Science | volume = 294 | issue = 5543 | pages = 797–99 | date = October 2001 | pmid = 11679654 | doi = 10.1126/science.1066315 }}</ref>
Studies on RNA interference earned a Nobel Prize for [[Andrew Z. Fire|Andrew Fire]] and [[Craig Mello]] in 2006, and another Nobel for studies on the transcription of RNA to [[Roger Kornberg]] in the same year. The discovery of gene regulatory RNAs has led to attempts to develop drugs made of RNA, such as [[siRNA]], to silence genes.<ref>{{cite journal | vauthors = Fichou Y, Férec C | title = The potential of oligonucleotides for therapeutic applications | journal = Trends in Biotechnology | volume = 24 | issue = 12 | pages = 563–70 | date = December 2006 | pmid = 17045686 | doi = 10.1016/j.tibtech.2006.10.003 }}</ref> Adding to the Nobel prizes for research on RNA, in 2009 it was awarded for the elucidation of the atomic structure of the ribosome to [[Venki Ramakrishnan]], [[Thomas A. Steitz]], and [[Ada Yonath]]. In 2023 the [[Nobel Prize in Physiology or Medicine]] was awarded to [[Katalin Karikó]] and [[Drew Weissman]] for their discoveries concerning [[Nucleoside analogue|modified nucleosides]] that enabled the development of effective mRNA vaccines against COVID-19.<ref>{{Cite web |title=The Nobel Prize in Physiology or Medicine 2023 |url=https://www.nobelprize.org/prizes/medicine/2023/press-release/ |access-date=2023-10-03 |website=NobelPrize.org |language=en-US}}</ref><ref>{{Cite news |date=2023-10-02 |title=Hungarian and US scientists win Nobel for COVID-19 vaccine discoveries |language=en |work=Reuters |url=https://www.reuters.com/article/nobel-prize-medicine-idCAKCN3120KJ |access-date=2023-10-03}}</ref><ref>{{Cite web |title=The Nobel Prize in Physiology or Medicine 2023 |url=https://www.nobelprize.org/prizes/medicine/2023/kariko/facts/ |access-date=2023-10-03 |website=NobelPrize.org |language=en-US}}</ref>
=== Relevance for prebiotic chemistry and abiogenesis ===
In 1968, [[Carl Woese]] hypothesized that RNA might be catalytic and suggested that the earliest forms of life (self-replicating molecules) could have relied on RNA both to carry genetic information and to catalyze biochemical reactions—an [[RNA world hypothesis|RNA world]].<ref>{{cite web|url=http://deposit.ddb.de/cgi-bin/dokserv?idn=982323891&dok_var=d1&dok_ext=pdf&filename=982323891.pdf|title=Common sequence structure properties and stable regions in RNA secondary structures|date=2006|work=Dissertation, Albert-Ludwigs-Universität, Freiburg im Breisgau|page=1|archive-url=https://web.archive.org/web/20120309212648/http://deposit.ddb.de/cgi-bin/dokserv?idn=982323891&dok_var=d1&dok_ext=pdf&filename=982323891.pdf|archive-date=March 9, 2012|url-status=dead|vauthors=Siebert S}}</ref><ref>{{cite journal | vauthors = Szathmáry E | title = The origin of the genetic code: amino acids as cofactors in an RNA world | journal = Trends in Genetics | volume = 15 | issue = 6 | pages = 223–29 | date = June 1999 | pmid = 10354582 | doi = 10.1016/S0168-9525(99)01730-8 }}</ref> In May 2022, scientists discovered that RNA can form spontaneously on prebiotic [[Volcanic glass|basalt lava glass]], presumed to have been abundant on the [[early Earth]].<ref name="AST-20220519">{{cite journal |author=Jerome, Craig A. |display-authors=et al. |title=Catalytic Synthesis of Polyribonucleic Acid on Prebiotic Rock Glasses |date=19 May 2022 |journal=[[Astrobiology (journal)|Astrobiology]] |volume=22 |issue=6 |pages=629–636 |doi=10.1089/ast.2022.0027 |pmid=35588195 |pmc=9233534 |bibcode=2022AsBio..22..629J |s2cid=248917871 }}</ref><ref name="PO-20220603">{{cite news |author=Foundation for Applied Molecular Evolution |title=Scientists announce a breakthrough in determining life's origin on Earth—and maybe Mars |url=https://phys.org/news/2022-06-scientists-breakthrough-life-earthand-mars.html |date=3 June 2022 |work=[[Phys.org]] |accessdate=3 June 2022 }}</ref>
In March 2015, [[DNA]] and RNA [[nucleobase]]s, including [[uracil]], [[cytosine]] and [[thymine]], were reportedly formed in the laboratory under [[outer space]] conditions, using starter chemicals such as [[pyrimidine]], an [[organic compound]] commonly found in [[meteorite]]s. [[Pyrimidine]], like [[polycyclic aromatic hydrocarbons]] (PAHs), is one of the most carbon-rich compounds found in the [[universe]] and may have been formed in [[red giant]]s or in [[Cosmic dust|interstellar dust]] and gas clouds.<ref name="NASA-20150303">{{cite web|url=http://www.nasa.gov/content/nasa-ames-reproduces-the-building-blocks-of-life-in-laboratory|title=NASA Ames Reproduces the Building Blocks of Life in Laboratory|last=Marlaire|first=Ruth|name-list-style=vanc|date=3 March 2015|work=[[NASA]]|access-date=5 March 2015|archive-date=5 March 2015|archive-url=https://web.archive.org/web/20150305083306/http://www.nasa.gov/content/nasa-ames-reproduces-the-building-blocks-of-life-in-laboratory/|url-status=dead}}</ref> In July 2022, astronomers reported massive amounts of [[Abiogenesis#Producing molecules: prebiotic synthesis|prebiotic molecule]]s, including possible RNA precursors, in the [[Galactic Center|galactic center]] of the [[Milky Way Galaxy]].<ref name="SA-20220708">{{cite news |last=Starr |first=Michelle |title=Loads of Precursors For RNA Have Been Detected in The Center of Our Galaxy |url=https://www.sciencealert.com/scientists-have-found-a-bunch-of-rna-precursors-in-the-galactic-center |date=8 July 2022 |work=[[ScienceAlert]] |accessdate=9 July 2022 }}</ref><ref name="FASS-20220708">{{cite journal |author=Rivilla, Victor M. |display-authors=et al. |title=Molecular Precursors of the RNA-World in Space: New Nitriles in the G+0.693–0.027 Molecular Cloud |date=8 July 2022 |journal=[[Frontiers in Astronomy and Space Sciences]] |volume=9 |page=876870 |doi=10.3389/fspas.2022.876870 |arxiv=2206.01053 |bibcode=2022FrASS...9.6870R |doi-access=free }}</ref>
== Medical applications ==
RNA, initially deemed unsuitable for therapeutics due to its short half-life, has been made useful through advances in stabilization. Therapeutic applications arise as RNA folds into complex conformations and binds proteins, nucleic acids, and small molecules to form catalytic centers.<ref>{{Cite journal |last1=Cech |first1=Thomas R. |last2=Steitz |first2=Joan A. |date=March 2014 |title=The Noncoding RNA Revolution—Trashing Old Rules to Forge New Ones |journal=Cell |volume=157 |issue=1 |pages=77–94 |doi=10.1016/j.cell.2014.03.008 |issn=0092-8674 |pmid=24679528 |s2cid=14852160 |doi-access=free}}</ref> RNA-based vaccines are thought to be easier to produce than traditional vaccines derived from killed or altered pathogens, because it can take months or years to grow and study a pathogen and determine which molecular parts to extract, inactivate, and use in a vaccine. Small molecules with conventional therapeutic properties can target RNA and DNA structures, thereby treating novel diseases. However, research is scarce on small molecules targeting RNA and approved drugs for human illness. Ribavirin, branaplam, and ataluren are currently available medications that stabilize double-stranded RNA structures and control splicing in a variety of disorders.<ref>{{Cite journal |last1=Palacino |first1=James |last2=Swalley |first2=Susanne E |last3=Song |first3=Cheng |last4=Cheung |first4=Atwood K |last5=Shu |first5=Lei |last6=Zhang |first6=Xiaolu |last7=Van Hoosear |first7=Mailin |last8=Shin |first8=Youngah |last9=Chin |first9=Donovan N |last10=Keller |first10=Caroline Gubser |last11=Beibel |first11=Martin |last12=Renaud |first12=Nicole A |last13=Smith |first13=Thomas M |last14=Salcius |first14=Michael |last15=Shi |first15=Xiaoying |date=2015-06-01 |title=SMN2 splice modulators enhance U1–pre-mRNA association and rescue SMA mice |url=|journal=Nature Chemical Biology |volume=11 |issue=7 |pages=511–517 |doi=10.1038/nchembio.1837 |issn=1552-4450 |pmid=26030728}}</ref><ref>{{Cite journal |last1=Roy |first1=Bijoyita |last2=Friesen |first2=Westley J. |last3=Tomizawa |first3=Yuki |last4=Leszyk |first4=John D. |last5=Zhuo |first5=Jin |last6=Johnson |first6=Briana |last7=Dakka |first7=Jumana |last8=Trotta |first8=Christopher R. |last9=Xue |first9=Xiaojiao |last10=Mutyam |first10=Venkateshwar |last11=Keeling |first11=Kim M. |last12=Mobley |first12=James A. |last13=Rowe |first13=Steven M. |last14=Bedwell |first14=David M. |last15=Welch |first15=Ellen M. |date=2016-10-04 |title=Ataluren stimulates ribosomal selection of near-cognate tRNAs to promote nonsense suppression |journal=Proceedings of the National Academy of Sciences |volume=113 |issue=44 |pages=12508–12513 |bibcode=2016PNAS..11312508R |doi=10.1073/pnas.1605336113 |issn=0027-8424 |pmc=5098639 |pmid=27702906 |doi-access=free}}</ref>
Protein-coding mRNAs have emerged as new therapeutic candidates, with RNA replacement being particularly beneficial for brief but torrential protein expression.<ref name="dx.doi.org">{{Cite journal |last1=Qadir |first1=Muhammad Imran |last2=Bukhat |first2=Sherien |last3=Rasul |first3=Sumaira |last4=Manzoor |first4=Hamid |last5=Manzoor |first5=Majid |date=2019-09-03 |title=RNA therapeutics: Identification of novel targets leading to drug discovery |url=|journal=Journal of Cellular Biochemistry |volume=121 |issue=2 |pages=898–929 |doi=10.1002/jcb.29364 |issn=0730-2312 |pmid=31478252 |s2cid=201806158}}</ref> In vitro transcribed mRNAs (IVT-mRNA) have been used to deliver proteins for bone regeneration, pluripotency, and heart function in animal models.<ref>{{Cite journal |last1=Balmayor |first1=Elizabeth R. |last2=Geiger |first2=Johannes P. |last3=Aneja |first3=Manish K. |last4=Berezhanskyy |first4=Taras |last5=Utzinger |first5=Maximilian |last6=Mykhaylyk |first6=Olga |last7=Rudolph |first7=Carsten |last8=Plank |first8=Christian |date=May 2016 |title=Chemically modified RNA induces osteogenesis of stem cells and human tissue explants as well as accelerates bone healing in rats |url=|journal=Biomaterials |volume=87 |pages=131–146 |doi=10.1016/j.biomaterials.2016.02.018 |issn=0142-9612 |pmid=26923361}}</ref><ref>{{Cite journal |last1=Plews |first1=Jordan R. |last2=Li |first2=JianLiang |last3=Jones |first3=Mark |last4=Moore |first4=Harry D. |last5=Mason |first5=Chris |last6=Andrews |first6=Peter W. |last7=Na |first7=Jie |date=2010-12-30 |title=Activation of Pluripotency Genes in Human Fibroblast Cells by a Novel mRNA Based Approach |journal=PLOS ONE |volume=5 |issue=12 |pages=e14397 |bibcode=2010PLoSO...514397P |doi=10.1371/journal.pone.0014397 |issn=1932-6203 |pmc=3012685 |pmid=21209933 |doi-access=free}}</ref><ref>{{Cite journal |last1=Preskey |first1=David |last2=Allison |first2=Thomas F. |last3=Jones |first3=Mark |last4=Mamchaoui |first4=Kamel |last5=Unger |first5=Christian |date=May 2016 |title=Synthetically modified mRNA for efficient and fast human iPS cell generation and direct transdifferentiation to myoblasts |url=|journal=Biochemical and Biophysical Research Communications |volume=473 |issue=3 |pages=743–751 |doi=10.1016/j.bbrc.2015.09.102 |issn=0006-291X |pmid=26449459}}</ref><ref>{{Cite journal |last1=Warren |first1=Luigi |last2=Manos |first2=Philip D. |last3=Ahfeldt |first3=Tim |last4=Loh |first4=Yuin-Han |last5=Li |first5=Hu |last6=Lau |first6=Frank |last7=Ebina |first7=Wataru |last8=Mandal |first8=Pankaj K. |last9=Smith |first9=Zachary D. |last10=Meissner |first10=Alexander |last11=Daley |first11=George Q. |last12=Brack |first12=Andrew S. |last13=Collins |first13=James J. |last14=Cowan |first14=Chad |last15=Schlaeger |first15=Thorsten M. |date=November 2010 |title=Highly Efficient Reprogramming to Pluripotency and Directed Differentiation of Human Cells with Synthetic Modified mRNA |url=|journal=Cell Stem Cell |volume=7 |issue=5 |pages=618–630 |doi=10.1016/j.stem.2010.08.012 |issn=1934-5909 |pmc=3656821 |pmid=20888316}}</ref><ref>{{Cite journal |last1=Elangovan |first1=Satheesh |last2=Khorsand |first2=Behnoush |last3=Do |first3=Anh-Vu |last4=Hong |first4=Liu |last5=Dewerth |first5=Alexander |last6=Kormann |first6=Michael |last7=Ross |first7=Ryan D. |last8=Rick Sumner |first8=D. |last9=Allamargot |first9=Chantal |last10=Salem |first10=Aliasger K. |date=November 2015 |title=Chemically modified RNA activated matrices enhance bone regeneration |url=|journal=Journal of Controlled Release |volume=218 |pages=22–28 |doi=10.1016/j.jconrel.2015.09.050 |issn=0168-3659 |pmc=4631704 |pmid=26415855}}</ref> SiRNAs, short RNA molecules, play a crucial role in innate defense against viruses and chromatin structure. They can be artificially introduced to silence specific genes, making them valuable for gene function studies, therapeutic target validation, and drug development.<ref name="dx.doi.org" />
[[mRNA vaccines]] have emerged as an important new class of vaccines, using mRNA to manufacture proteins which provoke an immune response. Their first successful large-scale application came in the form of [[COVID-19 vaccine]]s during the [[COVID-19 pandemic]].
== See also ==
{{Portal|Biology}}
{{Div col|colwidth=20em}}
* [[Biomolecular structure]]
* [[RNA virus]]
* [[DNA]]
* [[History of RNA biology|History of RNA Biology]]
* [[List of RNA biologists|List of RNA Biologists]]
* [[RNA Society]]
* [[Macromolecule]]
* [[RNA-based evolution]]
* [[Aptamer]]
* [[RNA origami]]
* [[Transcriptome]]
* [[RNA world hypothesis]]
{{Div col end}}
== References ==
{{Reflist|32em}}
== External links ==
{{wikiquote}}
{{Commons category|RNA}}
* [https://web.archive.org/web/20070314023716/http://www.imb-jena.de/RNA.html RNA World website] Link collection (structures, sequences, tools, journals)
* [https://web.archive.org/web/20071012034325/http://ndbserver.rutgers.edu/atlas/xray/ Nucleic Acid Database] Images of DNA, RNA, and complexes.
* [https://www.ibiology.org/biochemistry/rna-structure/ Anna Marie Pyle's Seminar: RNA Structure, Function, and Recognition]
{{Genetics|state=uncollapsed}}
{{Gene expression}}
{{RNA-footer}}
{{Nucleic acids}}
{{Authority control}}
{{DEFAULTSORT:Rna}}
[[Category:RNA| ]]
[[Category:RNA splicing]]
[[Category:Molecular biology]]
[[Category:Biotechnology]]
[[Category:Nucleic acids]]