Non-coding RNA 196493 225405194 2008-07-13T14:39:42Z ClueBot 4928500 Reverting possible vandalism by [[Special:Contributions/220.239.40.111|220.239.40.111]] to version by Narayanese. False positive? [[User:ClueBot/FalsePositives|Report it]]. Thanks, [[User:ClueBot]]. (439299) (Bot) :''"Srna" redirects here. For the Croatian footballer, see [[Darijo Srna]].'' A '''non-coding RNA''' ('''ncRNA''') is any [[RNA]] molecule that is not [[Translation (genetics)|translated]] into a [[protein]]. A previously used synonym, particularly with [[bacteria]], was '''small RNA''' ('''sRNA'''). However, some ncRNAs are very large (e.g. [[Xist gene|Xist]]). Less-frequently used synonyms are non-messenger RNA (nmRNA), small non-messenger RNA (snmRNA), or functional RNA (fRNA). The [[DNA]] sequence from which a non-coding RNA is transcribed as the end product is often called an '''RNA gene''' or non-coding RNA gene (see [[gene]]). Non-coding RNA genes include '''[[transfer RNA]]''' ('''[[tRNA]]''') and '''[[ribosomal RNA]]''' ('''[[rRNA]]'''), small RNAs such as [[snoRNA]]s, [[microRNA]]s, [[siRNA]]s and [[piRNA]]s and lastly long ncRNAs that include examples such as [[Xist]], Evf, Air, CTN and PINK. The number of ncRNAs encoded within the genome is unknown, however recent transcriptomic and microarray studies suggest the existence of over 30,000 long ncRNAs and at least as many small regulatory RNAs within the mouse genome alone. Since most of the newly identified ncRNAs have not been validated for their function, it is possible that the majority of them are meaningless (e.g. non-functional or truncated transcript). One of the major findings of the 2007 [[ENCODE]] Pilot Project was that "nearly the entire genome may be represented in primary transcripts that extensively overlap and include many non-protein-coding regions."<ref>{{cite journal | author=George M. Weinstock| title=ENCODE: More genomic empowerment| journal=Genome Research| year=2007| volume=17| pages=667–668| url=http://www.genome.org/cgi/content/full/17/6/667| doi=10.1101/gr.6534207| pmid=17567987}}</ref> == The evaluation of ncRNA has changed radically == It was formerly believed that the main role for RNA was to code for protein, though there were the recognized exceptions of rRNA (ribosomal), and tRNA (transfer). It was assumed that any leftover ncRNA which served none of those roles must usually be mere "junk" coding.{{huh}} Some might conceivably be coopted later by chance in the course of evolution, but it was otherwise assumed to be useless. There began to be signs that this was not true, e.g. with the paper by Brannan ''et al.'' (1990).<ref>Brannan, C.I., E.C.Dees, R.S.Ingram & S.M.Tilghman (1990). "The product of the H19 gene may function as an RNA". ''Molecular and Cellular Biology'', '''10'''(1), 28-36.</ref> Then by 2001, Mattick<ref>Mattick, J.S. (2001) "Noncoding RNAs: the architects of eukaryotic complexity". ''EMBO Reports'' '''2'''(11), 986-991. http://emboreports.npgjournals.com/cgi/content/full/2/11/986 </ref> had claimed that in fact this applied to '''more than 97%''' of the RNA produced from DNA. &nbsp; See also later works by Mattick and others.<ref>Mattick, J.S., & M.J.Gagen (2001). "The evolution of controlled multitask gene networks: The role of introns and other noncoding RNAs in the development of complex organisms". ''Mol. Biol. Evol.'' '''18'''(9), 1611-1630. ['''Review'''] http://mbe.oupjournals.org/cgi/content/full/18/9/1611 </ref><ref>Mattick, J.S. (2003). "Challenging the dogma: The hidden layer of non-protein-coding RNAs on complex organisms" ''Bioessays. '''25''', 930-939.[[http://www.imb-jena.de/jcb/journal_club/mattick2003.pdf]]</ref><ref>Mattick, J.S. (2004). "The hidden genetic program of complex organisms", ''Scientific American''. '''291'''(4), 30-37. [[http://www.sciam.com/article.cfm?articleID=00045BB6-5D49-1150-902F83414B7F4945]] </ref> —— &nbsp; Given this imbalance, it became clear that ncRNA must be playing other important roles; but what? == Newfound role — as "regulators" of various types == It has been becoming increasingly clear that cross-interactions between genes play a crucial role, and the importance of ncRNA for this task is explored in some detail in the table below. &nbsp; Rather less obvious is ncRNA's postulated role in how the brain deals with non-trivial thought processes, as follows: === Possible role as the most basic encodings for memory and behaviour === In developing his [[theory of cognitive development]], the late Professor [[Jean_Piaget|Piaget]] based his explanations on abstract constructs called "schemes". That leaves open just what these ''schemes'' might be in physical terms, though he did briefly consider the possibility of RNA in 1967.<ref>Piaget, J. (1967/1971). ''Biology and Knowledge''. Chicago University Press, and Edinburgh University Press.</ref> &nbsp; Such roles for RNA fell out of favour by about 1980 (partly because any such RNA was seen only as some sort of adjunct to synaptic change). &nbsp; Meanwhile, based on some work<ref>Traill, R.R. (1976 / 2007). ''Short papers and letters on the 'linear micro-element' theory of mental mechanism; and related questions of scientific method''. Ondwelle: Melbourne. [[http://www.ondwelle.com/OSM06.pdf]]</ref> from the 1970s, Traill (2005)<ref>Traill, R.R. (2005/2008) ''Thinking by molecule, synapse, or both? — From Piaget's schema, to the selecting/editing of ncRNA''. Ondwelle: Melbourne. http://www.ondwelle.com/OSM02.pdf </ref> argued that ''some sort of linear coding'' must underlie memory (at least for advanced thinking<ref>For advanced thinking (such as logic, symbolism, and speaking) the traditional synaptic mechanisms ''taken alone'' do not offer any explanation at all! Piaget's account does offer a plausible explanatory framework, and that seems consistent with ncRNA capabilities plus some other techical issues.</ref>), and that RNA is the only plausible candidate. &nbsp; Such an action-or-memory-encoding role need not conflict with the abovementioned "regulator" role. &nbsp; In fact ''"thought" itself might be seen as a special case of internal regulation''.<ref>or in other words, this notion (of "physical" regulation being closely related to "mental" regulation) looks very like the concept of "[[psychosomatic]] effects". — Traill, R.R. (2005, ''see above'') — pp.3&nbsp;and&nbsp;21.[[http://www.ondwelle.com/OSM02.pdf]] </ref> &nbsp; (Moreover this connection was perhaps already implied in the 1950s by [[William_Ross_Ashby|Ross Ashby]] when he argued that [[recursive]] elaborations to a simple [[homeostasis|homeostat]] could yield a brainlike system.<ref>Ashby, W.R. (1952 / 1960). ''Design for a Brain''. Chapman & Hall: London.</ref>) ==Distinction between functional RNA (fRNA) and ncRNA== The term ''ncRNA'' has been used, in addition to its [[ncRNA|above definition]], to describe regions of [[mRNA]] that are functional at the RNA level, i.e. they have a biological function other than coding for protein even though they are on a protein-coding mRNA, for example [[riboswitch|riboswitches]] and the [[SECIS element]]. They may even overlap with protein-coding sequence and are thus dual-functional: at the RNA level and at the protein level (e.g. [[SgrS RNA]] and [[RNAIII]]). However, these conflict with the [[OBO_Foundry|Sequence Ontology]]'s [http://www.sequenceontology.org/miSO/SO_CVS/ncRNA.html definition of ncRNA], which requires that a RNA does not contain ''any'' protein-coding sequence in order to be labeled ''ncRNA''. Several publications<ref> {{cite journal | author=Richard J. Carter, Inna Dubchak, Stephen R. Holbrook | title=A computational approach to identify genes for functional RNAs in genomic sequences | journal=Nucleic Acids Research | year=2001 | volume=29 | issue=19 | pages=3928–3938 | url=http://www.pubmedcentral.nih.gov.oca.ucsc.edu/articlerender.fcgi?artid=60242&rendertype=abstract }} </ref><ref> {{cite journal | author=Jakob Skou Pedersen, Gill Bejerano, Adam Siepel, Kate Rosenbloom, Kerstin Lindblad-Toh, Eric S. Lander, Jim Kent, Webb Miller, David Haussler | title=Identification and Classification of Conserved RNA Secondary Structures in the Human Genome | journal=PLOS Computational Biology | year=2006 | volume=2 | issue=4 | pages=e33 | url=http://compbiol.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pcbi.0020033 | doi=10.1371/journal.pcbi.0020033 }} </ref><ref> {{cite journal | author=Tomas Babak, Benjamin J Blencowe, Timothy R Hughes | title=Considerations in the identification of functional RNA structural elements in genomic alignments | journal=BMC Bioinformatics | year=2007 | issue=8 | pages=33 | url=http://www.pubmedcentral.nih.gov.oca.ucsc.edu/articlerender.fcgi?artid=1803800&rendertype=abstract | volume=8 | doi=10.1186/1471-2105-8-21 }} </ref> have started using the term '''functional RNA (fRNA)''', as opposed to ncRNA, to describe regions functional at the RNA level that may or may not be stand-alone RNA transcripts. Therefore, every ncRNA is a fRNA, but there exist fRNA (such as riboswitches, SECIS elements, and other cis-regulatory regions) that are not ncRNA. Yet the term fRNA could also include [[Messenger RNA|mRNA]] as this is RNA coding for protein and hence is functional. Additionally [[Systematic Evolution of Ligands by Exponential Enrichment|artificially evolved RNAs]] also fall under the fRNA umbrella term. Some publications<ref> {{cite journal | author=Sean Eddy | title=Non–coding RNA genes and the modern RNA world | journal=Nature Reviews Genetics | year=2001 | issue=2 | pages=919–929 | doi= 10.1038/35103511 | volume=2 }} </ref> state that the terms ''ncRNA'' and ''fRNA'' are nearly synonymous. ==Untranslated regions of mRNAs== {{Main|Five prime untranslated region|Three prime untranslated region}} Messenger RNA ([[mRNA]]) contains non-coding regions at its ends (called [[UTR]]s) which include [[riboswitch]]es and the [[SECIS element]]. Although UTRs do not code for protein, mRNA is not considered to be non-coding RNA. Many of the functional elements in UTRs are [[Cis-regulatory element|cis-regulatory elements]]. ==See also== * [[Ribozyme]] * [[List of RNAs]] ==References== <references/> ==External links== * [http://jsm-research.imb.uq.edu.au/rnadb Comprehensive database of mammalian ncRNAs] * [http://www.sanger.ac.uk/Software/Rfam/ The Rfam Database] A curated list of hundreds of families of related ncRNAs. Each family includes a multiple [[sequence alignment|alignment]] of known members, and predicted homologs in a large genome database. The definition of "family" is a pragmatic one, the goal being to lead to high-quality annotations. Thus, some families are quite broad (e.g. all tRNAs are in one family, as of 2004), while some families are quite narrow (e.g. there are many microRNA families, one for each type). * [http://wikiomics.org/wiki/List_of_articles#RNA Wikiomics/RNA] Provides links to a variety of ncRNA analysis tools for structure prediction, sequence alignment and homology search. * [http://www.noncode.org/ ncRNA database]NONCODE is a brand-new database of all kinds of noncoding RNAs (except tRNAs and rRNAs). {{Nucleic acids}} [[Category:RNA]] [[Category:Molecular genetics]] [[de:Non-coding RNA]] [[it:RNA non codificante]] [[ko:RRNA]] [[ja:ncRNA]] [[ur:غیر-رمزگر RNA]] [[zh:非編碼RNA]]