Editing RNA (section)

==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]] 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>