Non-coding RNA: Difference between revisions

Revision as of 22:42, 14 August 2022

Revision as of 23:21, 14 August 2022

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{{lead too short|date=January 2018}}

[[File:NcRNAs-central-dogma.svg|thumb|400x400px|The roles of non-coding RNAs in the [[central dogma of molecular biology]]: [[Ribonucleoprotein|Ribonucleoproteins]] are shown in red, non-coding RNAs in blue.]]

A '''non-coding RNA''' ('''ncRNA''') is an [[RNA]] molecule that is not [[Translation (genetics)|translated]] into a [[protein]]<ref name="pmid28696921">{{cite journal |vauthors=Monga I, Qureshi A, Thakur N, Gupta AK, Kumar M |year=2017 |title=ASPsiRNA: A Resource of ASP-siRNAs Having Therapeutic Potential for Human Genetic Disorders and Algorithm for Prediction of Their Inhibitory Efficacy |url=http://crdd.osdd.net/servers/aspsirna/asptar.php |journal=[[ G3 (Bethesda, Md.) ]] |volume=7 |issue=9 |pages=2931–2943 |doi=10.1534/g3.117.044024 |pmc=5592921 |pmid=28696921}}</ref>. The [[DNA]] sequence from which a functional non-coding RNA is transcribed is often called an RNA [[gene]]. Abundant and functionally important [[list of RNAs|types of non-coding RNAs]] include [[transfer RNA]]s (tRNAs) and [[ribosomal RNA]]s (rRNAs), as well as small RNAs such as [[microRNA]]s, [[siRNA]]s, [[piRNA]]s, [[snoRNA]]s, [[snRNA]]s, [[Extracellular RNA|exRNAs]], [[scaRNAs]] and the [[long noncoding RNA|long ncRNA]]s such as [[Xist]] and [[HOTAIR]].

The number of non-coding RNAs within the human genome is unknown; however, recent [[Transcriptomics|transcriptomic]] and [[Bioinformatics|bioinformatic]] studies suggest that there are thousands of them.<ref name="pmid15790807">{{cite journal | vauthors = Cheng J, Kapranov P, Drenkow J, Dike S, Brubaker S, Patel S, Long J, Stern D, Tammana H, Helt G, Sementchenko V, Piccolboni A, Bekiranov S, Bailey DK, Ganesh M, Ghosh S, Bell I, Gerhard DS, Gingeras TR | display-authors = 6 | title = Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution | journal = Science | volume = 308 | issue = 5725 | pages = 1149–54 | date = May 2005 | pmid = 15790807 | doi = 10.1126/science.1108625 | bibcode = 2005Sci...308.1149C | s2cid = 13047538 }}</ref><ref name="pmid17571346" /><ref name="Thind">{{cite journal | vauthors = Thind AS, Monga I, Thakur PK, Kumari P, Dindhoria K, Krzak M, Ranson M, Ashford B| title = Demystifying emerging bulk RNA-Seq applications: the application and utility of bioinformatic methodology | journal = Briefings in Bioinformatics | volume = 22 | issue = 6 | date = Nov 2021 | pmid = 34329375 | doi = 10.1093/bib/bbab259}}</ref><ref name="pmid17568003">{{cite journal | vauthors = Washietl S, Pedersen JS, Korbel JO, Stocsits C, Gruber AR, Hackermüller J, Hertel J, Lindemeyer M, Reiche K, Tanzer A, Ucla C, Wyss C, Antonarakis SE, Denoeud F, Lagarde J, Drenkow J, Kapranov P, Gingeras TR, Guigó R, Snyder M, Gerstein MB, Reymond A, Hofacker IL, Stadler PF | display-authors = 6 | title = Structured RNAs in the ENCODE selected regions of the human genome | journal = Genome Research | volume = 17 | issue = 6 | pages = 852–64 | date = June 2007 | pmid = 17568003 | pmc = 1891344 | doi = 10.1101/gr.5650707 }}</ref><ref name= MorrisKV>{{cite book | veditors = Morris KV | year=2012 | title=Non-coding RNAs and Epigenetic Regulation of Gene Expression: Drivers of Natural Selection | publisher=[[Caister Academic Press]] | isbn= 978-1-904455-94-3}}</ref><ref name="Shahrouki P 2012">{{cite journal | vauthors = Shahrouki P, Larsson E | title = The non-coding oncogene: a case of missing DNA evidence? | journal = Frontiers in Genetics | volume = 3 | pages = 170 | date = 2012 | pmid = 22988449 | pmc = 3439828 | doi = 10.3389/fgene.2012.00170 | doi-access = free }}</ref><!--^{but see}--><ref>{{cite journal | vauthors = van Bakel H, Nislow C, Blencowe BJ, Hughes TR | title = Most "dark matter" transcripts are associated with known genes | journal = PLOS Biology | volume = 8 | issue = 5 | pages = e1000371 | date = May 2010 | pmid = 20502517 | pmc = 2872640 | doi = 10.1371/journal.pbio.1000371 | editor1-last = Eddy | editor1-first = Sean R. }}</ref><ref name="Qureshi bau103">{{cite journal |vauthors=Qureshi A, Thakur N, Monga I, Thakur A, Kumar M |date=1 January 2014 |title=VIRmiRNA: a comprehensive resource for experimentally validated viral miRNAs and their targets |journal=Database |volume=2014 |pages=bau103 |doi=10.1093/database/bau103 |pmc=4224276 |pmid=25380780}}</ref> Many of the newly identified ncRNAs have not been validated for their function.<ref name="pmid15851066">{{cite journal | vauthors = Hüttenhofer A, Schattner P, Polacek N | title = Non-coding RNAs: hope or hype? | journal = Trends in Genetics | volume = 21 | issue = 5 | pages = 289–97 | date = May 2005 | pmid = 15851066 | doi = 10.1016/j.tig.2005.03.007 }}</ref> It is also likely that many ncRNAs are non functional (sometimes referred to as '''junk RNA'''), and are the product of spurious transcription.<ref name="waste">{{cite journal | vauthors = Brosius J | title = Waste not, want not--transcript excess in multicellular eukaryotes | journal = Trends in Genetics | volume = 21 | issue = 5 | pages = 287–8 | date = May 2005 | pmid = 15851065 | doi = 10.1016/j.tig.2005.02.014 }}</ref><ref name="PalazzoLee2015">{{cite journal | vauthors = Palazzo AF, Lee ES | title = Non-coding RNA: what is functional and what is junk? | journal = Frontiers in Genetics | volume = 6 | pages = 2 | year = 2015 | pmid = 25674102 | pmc = 4306305 | doi = 10.3389/fgene.2015.00002 | doi-access = free }}</ref>

Non-coding RNAs are thought to contribute to diseases including [[cancer]] and [[Alzheimer's]].

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===Cancer===

Many ncRNAs show abnormal expression patterns in [[cancer]]ous tissues.<ref name="Shahrouki P 2012"/> These include [[microRNA|miRNAs]] <ref name="Qureshi bau1032">{{cite journal |vauthors=Qureshi A, Thakur N, Monga I, Thakur A, Kumar M |date=1 January 2014 |title=VIRmiRNA: a comprehensive resource for experimentally validated viral miRNAs and their targets |journal=Database |volume=2014 |pages=bau103 |doi=10.1093/database/bau103 |pmc=4224276 |pmid=25380780}}</ref>, [[Long noncoding RNA#Long non-coding RNAs in disease|long mRNA-like ncRNAs]],<ref name="pmid11890990">{{cite journal | vauthors = Pibouin L, Villaudy J, Ferbus D, Muleris M, Prospéri MT, Remvikos Y, Goubin G | title = Cloning of the mRNA of overexpression in colon carcinoma-1: a sequence overexpressed in a subset of colon carcinomas | journal = Cancer Genetics and Cytogenetics | volume = 133 | issue = 1 | pages = 55–60 | date = February 2002 | pmid = 11890990 | doi = 10.1016/S0165-4608(01)00634-3 }}</ref><ref name="pmid16569192">{{cite journal | vauthors = Fu X, Ravindranath L, Tran N, Petrovics G, Srivastava S | title = Regulation of apoptosis by a prostate-specific and prostate cancer-associated noncoding gene, PCGEM1 | journal = DNA and Cell Biology | volume = 25 | issue = 3 | pages = 135–41 | date = March 2006 | pmid = 16569192 | doi = 10.1089/dna.2006.25.135 }}</ref> [[GAS5]],<ref name="pmid18836484">{{cite journal | vauthors = Mourtada-Maarabouni M, Pickard MR, Hedge VL, Farzaneh F, Williams GT | title = GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer | journal = Oncogene | volume = 28 | issue = 2 | pages = 195–208 | date = January 2009 | pmid = 18836484 | doi = 10.1038/onc.2008.373 | doi-access = free }}</ref> [[Small nucleolar RNA SNORD50|SNORD50]],<ref name="pmid19683667">{{cite journal | vauthors = Dong XY, Guo P, Boyd J, Sun X, Li Q, Zhou W, Dong JT | title = Implication of snoRNA U50 in human breast cancer | journal = Journal of Genetics and Genomics = Yi Chuan Xue Bao | volume = 36 | issue = 8 | pages = 447–54 | date = August 2009 | pmid = 19683667 | pmc = 2854654 | doi = 10.1016/S1673-8527(08)60134-4 }}</ref> [[telomerase RNA]] and [[Y RNA]]s.<ref name="pmid18283318">{{cite journal | vauthors = Christov CP, Trivier E, Krude T | title = Noncoding human Y RNAs are overexpressed in tumours and required for cell proliferation | journal = British Journal of Cancer | volume = 98 | issue = 5 | pages = 981–8 | date = March 2008 | pmid = 18283318 | pmc = 2266855 | doi = 10.1038/sj.bjc.6604254 }}</ref> The miRNAs are involved in the large scale regulation of many protein coding genes,<ref name="pmid16308420">{{cite journal | vauthors = Farh KK, Grimson A, Jan C, Lewis BP, Johnston WK, Lim LP, Burge CB, Bartel DP | title = The widespread impact of mammalian MicroRNAs on mRNA repression and evolution | journal = Science | volume = 310 | issue = 5755 | pages = 1817–21 | date = December 2005 | pmid = 16308420 | doi = 10.1126/science.1121158 | bibcode = 2005Sci...310.1817F | s2cid = 1849875 }}</ref><ref name="pmid15685193">{{cite journal | vauthors = Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM | title = Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs | journal = Nature | volume = 433 | issue = 7027 | pages = 769–73 | date = February 2005 | pmid = 15685193 | doi = 10.1038/nature03315 | bibcode = 2005Natur.433..769L | s2cid = 4430576 }}</ref> the Y RNAs are important for the initiation of DNA replication,<ref name="pmid16943439"/> telomerase RNA that serves as a primer for telomerase, an RNP that extends [[Telomere|telomeric regions]] at chromosome ends (see [[Telomere#Human telomeres.2C cancer.2C and ALT.|telomeres and disease]] for more information). The direct function of the long mRNA-like ncRNAs is less clear.

[[Germ-line]] mutations in [[Mir-16 microRNA precursor family|miR-16-1]] and [[Mir-15 microRNA precursor family|miR-15]] primary precursors have been shown to be much more frequent in patients with [[chronic lymphocytic leukemia]] compared to control populations.<ref name="pmid16251535">{{cite journal | vauthors = Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM | title = A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia | journal = The New England Journal of Medicine | volume = 353 | issue = 17 | pages = 1793–801 | date = October 2005 | pmid = 16251535 | doi = 10.1056/NEJMoa050995 }}</ref><ref>{{cite journal | vauthors = Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM | title = Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 24 | pages = 15524–9 | date = November 2002 | pmid = 12434020 | pmc = 137750 | doi = 10.1073/pnas.242606799 | bibcode = 2002PNAS...9915524C | doi-access = free }}</ref>