Editing MicroRNA (section)

{{short description|Small non-coding ribonucleic acid molecule}}
{{Hatnote|Not to be confused with [[mitochondrial DNA]] (m(t)DNA); or [[messenger RNA]] (mRNA).}}
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{{DISPLAYTITLE:microRNA}}
[[File:MiRNA.svg|thumb|400px|Pre-miRNA instead of Pri-miRNA in the first point of mechanism. Diagram of microRNA (miRNA) action with [[mRNA]]]]
[[File:Examples of microRNA stem-loops.jpg|thumb|400px|Examples of miRNA hairpins ([[stem-loop]]s), with the mature miRNAs shown in red]]

'''Micro ribonucleic acid''' ('''microRNA''', '''miRNA''', '''μRNA''') are small, single-stranded, [[non-coding RNA]] molecules containing 21–23&nbsp;[[nucleotide]]s.<ref name="Metazoan MicroRNAs">{{cite journal | vauthors = Bartel DP | title = Metazoan MicroRNAs | journal = Cell | volume = 173 | issue = 1 | pages = 20–51 | date = March 2018 | pmid = 29570994 | pmc = 6091663 | doi = 10.1016/j.cell.2018.03.006 }}</ref> Found in plants, animals, and even some viruses, miRNAs are involved in [[RNA silencing]] and post-transcriptional [[regulation of gene expression]].<ref name=pmid14744438>{{cite journal | vauthors = Bartel DP | date = January 2004 | title = MicroRNAs: genomics, biogenesis, mechanism, and function | journal = Cell | volume = 116 | issue = 2 | pages = 281–297 | pmid = 14744438 | doi = 10.1016/S0092-8674(04)00045-5 | doi-access = free }}</ref><ref name="Qureshi bau103">{{cite journal |vauthors=Qureshi A, Thakur N, Monga I, Thakur A, Kumar M |date=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> miRNAs [[base-pair]] to complementary sequences in [[messenger RNA]] (mRNA) molecules,<ref name=pmid19167326>{{cite journal | vauthors = Bartel DP | title = MicroRNAs: Target recognition and regulatory functions | journal = [[Cell (journal)|Cell]] | volume = 136 | issue = 2 | pages = 215–233 | date = January 2009 | pmid = 19167326 | pmc = 3794896 | doi = 10.1016/j.cell.2009.01.002 }}</ref> then [[Gene silencing|silence]] said [[mRNA]] molecules by one or more of the following processes:<ref name="Metazoan MicroRNAs"/><ref>{{cite journal | vauthors = Jonas S, Izaurralde E | title = Towards a molecular understanding of microRNA-mediated gene silencing | journal = Nature Reviews. Genetics | volume = 16 | issue = 7 | pages = 421–433 | date = July 2015 | pmid = 26077373 | doi = 10.1038/nrg3965 | s2cid = 24892348 }}</ref>

* Cleaving the mRNA strand into two pieces.
* Destabilizing the mRNA by shortening its [[polyadenylation|poly(A) tail]].
* Reducing [[translation (biology)|translation]] of the mRNA into proteins.

In cells of humans and other animals, miRNAs primarily act by destabilizing the mRNA.<ref>{{cite journal | vauthors = Jonas S, Izaurralde E | date = July 2015 | title = Towards a molecular understanding of microRNA-mediated gene silencing | journal = Nature Reviews. Genetics | volume = 16 | issue = 7 | pages = 421–433 | pmid = 26077373 | doi = 10.1038/nrg3965 | s2cid = 24892348 }}</ref><ref>{{cite journal | vauthors = Guo H, Ingolia NT, Weissman JS, Bartel DP | title = Mammalian microRNAs predominantly act to decrease target mRNA levels | journal = Nature | volume = 466 | issue = 7308 | pages = 835–840 | date = August 2010 | pmid = 20703300 | pmc = 2990499 | doi = 10.1038/nature09267 | hdl-access = free | bibcode = 2010Natur.466..835G | hdl = 1721.1/72447 }}</ref>

miRNAs resemble the [[small interfering RNA|small interfering RNAs (siRNAs)]] of the [[RNA interference|RNA interference (RNAi)]] pathway, except miRNAs derive from regions of RNA transcripts that fold back on themselves to form short [[stem-loop]]s (hairpins), whereas siRNAs derive from longer regions of [[double-stranded RNA]].<ref name=pmid14744438/> The [[human genome]] may encode over 1900 miRNAs,<ref>{{cite web |title=''Homo sapiens'' miRNAs |series=miRBase |publisher=[[Manchester University]] |place=Manchester, UK |url=http://www.mirbase.org/cgi-bin/mirna_summary.pl?org=hsa }}</ref><ref name="Alles et al., 2019 - estimate of number of human miRNAs">{{cite journal | vauthors = Alles J, Fehlmann T, Fischer U, Backes C, Galata V, Minet M, Hart M, Abu-Halima M, Grässer FA, Lenhof HP, Keller A, Meese E |display-authors=6 | date = April 2019 | title = An estimate of the total number of true human miRNAs | journal = [[Nucleic Acids Research]] | volume = 47 | issue = 7 | pages = 3353–3364 | pmid = 30820533 | pmc = 6468295 | doi = 10.1093/nar/gkz097 }}</ref> However, only about 500&nbsp;human miRNAs represent ''[[bona fide]]'' miRNAs in the manually curated miRNA gene database [[MirGeneDB]].<ref name="Fromm et al., 2020 - MirGeneDB 2.0">{{cite journal | vauthors = Fromm B, Domanska D, Høye E, Ovchinnikov V, Kang W, Aparicio-Puerta E, Johansen M, Flatmark K, Mathelier A, Hovig E, Hackenberg M, Friedländer MR, Peterson KJ |display-authors=6 | date = January 2020 | title = MirGeneDB&nbsp;2.0: The metazoan microRNA complement | journal = [[Nucleic Acids Research]] | volume = 48 | issue = D1 | pages = D132–D141 | pmid = 31598695 | pmc = 6943042 | doi = 10.1093/nar/gkz885 }}</ref>

miRNAs are abundant in many mammalian cell types.<ref name="pmid12672692">{{cite journal | vauthors = Lim LP, Lau NC, Weinstein EG, Abdelhakim A, Yekta S, Rhoades MW, Burge CB, Bartel DP |display-authors=6 | date = April 2003 | title = The microRNAs of ''Caenorhabditis elegans'' | journal = [[Genes & Development]] | volume = 17 | issue = 8 | pages = 991–1008 | pmid = 12672692 | pmc = 196042 | doi = 10.1101/gad.1074403 }}</ref><ref name="pmid12007417">{{cite journal | vauthors = Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T | date = April 2002 | title = Identification of tissue-specific microRNAs from mouse | journal = Current Biology | volume = 12 | issue = 9 | pages = 735–739 | pmid = 12007417 | doi = 10.1016/S0960-9822(02)00809-6 | doi-access = free | bibcode = 2002CBio...12..735L }}</ref> They appear to target about 60% of the genes of humans and other mammals.<ref name="Lewis BP, Burge CB, Bartel DP 2005 15–20">{{cite journal | vauthors = Lewis BP, Burge CB, Bartel DP | date = January 2005 | title = Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets | journal = Cell | volume = 120 | issue = 1 | pages = 15–20 | pmid = 15652477 | doi = 10.1016/j.cell.2004.12.035 | doi-access = free }}</ref><ref name=pmid18955434>{{cite journal | vauthors = Friedman RC, Farh KK, Burge CB, Bartel DP | date = January 2009 | title = Most mammalian mRNAs are conserved targets of microRNAs | journal = Genome Research | volume = 19 | issue = 1 | pages = 92–105 | pmid = 18955434 | pmc = 2612969 | doi = 10.1101/gr.082701.108 }}</ref> Many miRNAs are evolutionarily conserved, which implies that they have important biological functions.<ref name=ReferenceD>{{cite journal | vauthors = Fromm B, Billipp T, Peck LE, Johansen M, Tarver JE, King BL, Newcomb JM, Sempere LF, Flatmark K, Hovig E, Peterson KJ |display-authors=6 | year = 2015 | title = A uniform system for the annotation of vertebrate microRNA genes and the evolution of the human microRNAome | journal = [[Annual Review of Genetics]] | volume = 49 |issue=1 | pages = 213–242 | pmid = 26473382 | pmc = 4743252 | doi = 10.1146/annurev-genet-120213-092023 |bibcode=2015ARGen..49..213F }}</ref><ref name="Metazoan MicroRNAs"/> For example, 90 families of miRNAs have been conserved since at least the common ancestor of mammals and fish, and most of these conserved miRNAs have important functions, as shown by studies in which genes for one or more members of a family have been knocked out in mice.<ref name="Metazoan MicroRNAs"/>

In 2024, American scientists [[Victor Ambros]] and [[Gary Ruvkun]] were awarded the [[Nobel Prize in Physiology or Medicine]] for their work on the discovery of miRNA and its role in [[Post-transcriptional regulation|post-transcriptional gene regulation]].<ref>{{cite web | url=https://www.nobelprize.org/prizes/medicine/2024/advanced-information/ | title=The Nobel Prize in Physiology or Medicine 2024 }}</ref><ref>{{cite press release |title=The Nobel Prize in Physiology or Medicine 2024 |website=NobelPrize.org |url=https://www.nobelprize.org/prizes/medicine/2024/press-release/ |access-date=2024-10-07 |lang=en-US}}</ref><ref>{{cite news |last=Lewis |first=Tanya |date=7 October 2024 |title=Nobel Prize in Physiology or Medicine awarded for discovery of microRNA gene regulation |magazine=[[Scientific American]]  |url=https://www.scientificamerican.com/article/nobel-prize-in-physiology-or-medicine-awarded-for-discovery-of-microrna-gene/ |access-date=2024-10-07 |language=en-US}}</ref>

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