Non-coding RNA: Difference between revisions

Revision as of 17:23, 2 September 2022

Revision as of 20:50, 28 September 2022

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A '''non-coding RNA''' ('''ncRNA''') is an [[RNA]] molecule that is not [[Translation (genetics)|translated]] into a [[protein]]. 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> 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> There is no consensus in the literature on how much of it is functional. Some researchers have argued that many ncRNAs are non-functional (sometimes referred to as "junk RNA"), spurious transcriptions.<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> Others, however, disagree, arguing instead that many of the current ncRNAs do have functions and that those functions are being and will continue to be discovered.<ref>{{cite book |last1=Mattick |first1=John |last2=Amaral |first2=Paulo |title=RNA, The Epicenter of Genetic Information : A New Understanding of Molecular Biology |date=2022 |publisher=CRC Press |isbn= 9780367623920}}</ref><ref>{{cite journal |last1=Lee |first1=Hyunmin |last2=Zhang |first2=Zhaolei |last3=Krause |first3=Henry M. |title=Long Noncoding RNAs and Repetitive Elements: Junk or Intimate Evolutionary Partners? |journal=Trends in Genetics |date=December 2019 |volume=35 |issue=12 |pages=892–902 |doi=10.1016/j.tig.2019.09.006|pmid=31662190 |s2cid=204975291 }}</ref>

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

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==Biological roles==

Noncoding RNAs belong to several groups and are involved in many cellular processes.<ref name="Monga">{{cite journal | vauthors = Monga I, Banerjee I| title = Computational Identification of piRNAs Using Features Based on RNA Sequence, Structure, Thermodynamic and Physicochemical Properties | journal = Current Genomics | volume = 20 | issue = 7 | pages = 508–518 | date = November 2019 | pmid = 32655289| doi = 10.2174/1389202920666191129112705 | pmc = 7327968 }}</ref> These range from ncRNAs of central importance that are conserved across all or most cellular life through to more transient ncRNAs specific to one or a few closely related species. The more conserved ncRNAs are thought to be molecular fossils or relics from the [[LUCA|last universal common ancestor]] and the [[RNA world hypothesis|RNA world]], and their current roles remain mostly in regulation of information flow from DNA to protein.<ref name="pmid9419222">{{cite journal | vauthors = Jeffares DC, Poole AM, Penny D | title = Relics from the RNA world | journal = Journal of Molecular Evolution | volume = 46 | issue = 1 | pages = 18–36 | date = January 1998 | pmid = 9419222 | doi = 10.1007/PL00006280 | bibcode = 1998JMolE..46...18J | s2cid = 2029318 }}</ref><ref name="pmid9419221">{{cite journal | vauthors = Poole AM, Jeffares DC, Penny D | title = The path from the RNA world | journal = Journal of Molecular Evolution | volume = 46 | issue = 1 | pages = 1–17 | date = January 1998 | pmid = 9419221 | doi = 10.1007/PL00006275 | bibcode = 1998JMolE..46....1P | s2cid = 17968659 }}</ref><ref name="pmid10497339">{{cite journal | vauthors = Poole A, Jeffares D, Penny D | title = Early evolution: prokaryotes, the new kids on the block | journal = BioEssays | volume = 21 | issue = 10 | pages = 880–9 | date = October 1999 | pmid = 10497339 | doi = 10.1002/(SICI)1521-1878(199910)21:10<880::AID-BIES11>3.0.CO;2-P | s2cid = 45607498 }}</ref>

===In translation===

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''Bifunctional RNAs'', or ''dual-function RNAs'', are RNAs that have two distinct functions.<ref name="pmid18042713">{{cite journal | vauthors = Wadler CS, Vanderpool CK | title = A dual function for a bacterial small RNA: SgrS performs base pairing-dependent regulation and encodes a functional polypeptide | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 51 | pages = 20454–9 | date = December 2007 | pmid = 18042713 | pmc = 2154452 | doi = 10.1073/pnas.0708102104 | bibcode = 2007PNAS..10420454W | doi-access = free }}</ref><ref name="pmid19043537">{{cite journal | vauthors = Dinger ME, Pang KC, Mercer TR, Mattick JS | title = Differentiating protein-coding and noncoding RNA: challenges and ambiguities | journal = PLOS Computational Biology | volume = 4 | issue = 11 | pages = e1000176 | date = November 2008 | pmid = 19043537 | pmc = 2518207 | doi = 10.1371/journal.pcbi.1000176 | editor1-last = McEntyre | bibcode = 2008PLSCB...4E0176D | editor1-first = Johanna }}</ref> The majority of the known bifunctional RNAs are mRNAs that encode both a protein and ncRNAs. However, a growing number of ncRNAs fall into two different ncRNA categories; e.g., [[snoRNA|H/ACA box snoRNA]] and [[miRNA]].<ref name="pmid19043559">{{cite journal | vauthors = Saraiya AA, Wang CC | title = snoRNA, a novel precursor of microRNA in Giardia lamblia | journal = PLOS Pathogens | volume = 4 | issue = 11 | pages = e1000224 | date = November 2008 | pmid = 19043559 | pmc = 2583053 | doi = 10.1371/journal.ppat.1000224 | editor1-last = Goldberg | editor1-first = Daniel Eliot }}</ref><ref name="pmid19026782">{{cite journal | vauthors = Ender C, Krek A, Friedländer MR, Beitzinger M, Weinmann L, Chen W, Pfeffer S, Rajewsky N, Meister G | title = A human snoRNA with microRNA-like functions | journal = Molecular Cell | volume = 32 | issue = 4 | pages = 519–28 | date = November 2008 | pmid = 19026782 | doi = 10.1016/j.molcel.2008.10.017 }}</ref>

Two well known examples of bifunctional RNAs are [[SgrS RNA]] and [[RNAIII]]. However, a handful of other bifunctional RNAs are known to exist (e.g., steroid receptor activator/SRA,<ref name="pmid17710122">{{cite journal | vauthors = Leygue E | title = Steroid receptor RNA activator (SRA1): unusual bifaceted gene products with suspected relevance to breast cancer | journal = Nuclear Receptor Signaling | volume = 5 | pages = e006 | date = August 2007 | pmid = 17710122 | pmc = 1948073 | doi = 10.1621/nrs.05006 }}</ref> VegT RNA,<ref name="pmid9012531">{{cite journal | vauthors = Zhang J, King ML | title = Xenopus VegT RNA is localized to the vegetal cortex during oogenesis and encodes a novel T-box transcription factor involved in mesodermal patterning | journal = Development | volume = 122 | issue = 12 | pages = 4119–29 | date = December 1996 | doi = 10.1242/dev.122.12.4119 | pmid = 9012531 | s2cid = 28462527 }}</ref><ref name="pmid16000384">{{cite journal | vauthors = Kloc M, Wilk K, Vargas D, Shirato Y, Bilinski S, Etkin LD | title = Potential structural role of non-coding and coding RNAs in the organization of the cytoskeleton at the vegetal cortex of Xenopus oocytes | journal = Development | volume = 132 | issue = 15 | pages = 3445–57 | date = August 2005 | pmid = 16000384 | doi = 10.1242/dev.01919 | doi-access = free }}</ref>

Oskar RNA,<ref name="pmid16835436">{{cite journal | vauthors = Jenny A, Hachet O, Závorszky P, Cyrklaff A, Weston MD, Johnston DS, Erdélyi M, Ephrussi A | title = A translation-independent role of oskar RNA in early Drosophila oogenesis | journal = Development | volume = 133 | issue = 15 | pages = 2827–33 | date = August 2006 | pmid = 16835436 | doi = 10.1242/dev.02456 | doi-access = free }}</ref> [[ENOD40]],<ref name="pmid17452360">{{cite journal | vauthors = Gultyaev AP, Roussis A | title = Identification of conserved secondary structures and expansion segments in enod40 RNAs reveals new enod40 homologues in plants | journal = Nucleic Acids Research | volume = 35 | issue = 9 | pages = 3144–52 | year = 2007 | pmid = 17452360 | pmc = 1888808 | doi = 10.1093/nar/gkm173 }}</ref> p53 RNA<ref name="pmid19160491">{{cite journal | vauthors = Candeias MM, Malbert-Colas L, Powell DJ, Daskalogianni C, Maslon MM, Naski N, Bourougaa K, Calvo F, Fåhraeus R | title = P53 mRNA controls p53 activity by managing Mdm2 functions | journal = Nature Cell Biology | volume = 10 | issue = 9 | pages = 1098–105 | date = September 2008 | pmid = 19160491 | doi = 10.1038/ncb1770 | s2cid = 5122088 }}</ref> and [[SR1 RNA]].<ref>{{cite journal | vauthors = Gimpel M, Preis H, Barth E, Gramzow L, Brantl S | title = SR1--a small RNA with two remarkably conserved functions | journal = Nucleic Acids Research | volume = 40 | issue = 22 | pages = 11659–72 | date = December 2012 | pmid = 23034808 | pmc = 3526287 | doi = 10.1093/nar/gks895 }}</ref> Bifunctional RNAs have recently been the subject of a special issue of [[Biochimie]].<ref>{{cite journal | vauthors = Francastel C, Hubé F | title = Coding or non-coding: Need they be exclusive? | journal = Biochimie | volume = 93 | issue = 11 | pages = vi–vii | date = November 2011 | pmid = 21963143 | doi = 10.1016/S0300-9084(11)00322-1 | url = https://zenodo.org/record/889579 }}</ref>

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The [[p53]] tumor suppressor is arguably the most important agent in preventing tumor formation and progression. The p53 protein functions as a transcription factor with a crucial role in orchestrating the cellular stress response. In addition to its crucial role in cancer, p53 has been implicated in other diseases including diabetes, cell death after ischemia, and various neurodegenerative diseases such as Huntington, Parkinson, and Alzheimer. Studies have suggested that p53 expression is subject to regulation by non-coding RNA.<ref name="MorrisKV"/>

Another example of non-coding RNA dysregulated in cancer cells is the long non-coding RNA Linc00707. Linc00707 is upregulated and sponges miRNAs in human bone marrow-derived mesenchymal stem cells,<ref>{{Cite journal|last1=Jia|first1=Bo|last2=Wang|first2=Zhiping|last3=Sun|first3=Xiang|last4=Chen|first4=Jun|last5=Zhao|first5=Jianjiang|last6=Qiu|first6=Xiaoling|date=December 2019|title=Long noncoding RNA LINC00707 sponges miR-370-3p to promote osteogenesis of human bone marrow-derived mesenchymal stem cells through upregulating WNT2B|url= |journal=Stem Cell Research & Therapy|language=en|volume=10|issue=1|pages=67|doi=10.1186/s13287-019-1161-9|issn=1757-6512|pmc=6387535|pmid=30795799}}</ref> in hepatocellular carcinoma,<ref>{{Cite journal|last1=Tu|first1=Jianfei|last2=Zhao|first2=Zhongwei|last3=Xu|first3=Min|last4=Chen|first4=Minjiang|last5=Weng|first5=Qiaoyou|last6=Wang|first6=Jiangmei|last7=Ji|first7=Jiansong|date=July 2019|title=LINC00707 contributes to hepatocellular carcinoma progression via sponging miR‐206 to increase CDK14|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.27737|journal=Journal of Cellular Physiology|language=en|volume=234|issue=7|pages=10615–10624|doi=10.1002/jcp.27737|pmid=30488589|s2cid=54119752|issn=0021-9541}}</ref> gastric cancer<ref>{{Cite journal|last1=Xie|first1=Min|last2=Ma|first2=Tianshi|last3=Xue|first3=Jiangyang|last4=Ma|first4=Hongwei|last5=Sun|first5=Ming|last6=Zhang|first6=Zhihong|last7=Liu|first7=Minjuan|last8=Liu|first8=Yinghua|last9=Ju|first9=Songwen|last10=Wang|first10=Zhaoxia|last11=De|first11=Wei|date=February 2019|title=The long intergenic non-protein coding RNA 707 promotes proliferation and metastasis of gastric cancer by interacting with mRNA stabilizing protein HuR|url=https://linkinghub.elsevier.com/retrieve/pii/S0304383518306980|journal=Cancer Letters|language=en|volume=443|pages=67–79|doi=10.1016/j.canlet.2018.11.032|pmid=30502359|s2cid=54611497}}</ref> or breast cancer,<ref>{{Cite journal|last1=Li|first1=Tong|last2=Li|first2=Yunpeng|last3=Sun|first3=Hongyan|date=2019-06-06|title=MicroRNA-876 is sponged by long noncoding RNA LINC00707 and directly targets metadherin to inhibit breast cancer malignancy|url= |journal=Cancer Management and Research|volume=11|pages=5255–5269|language=en|doi=10.2147/cmar.s210845|pmc=6559252|pmid=31239777}}</ref><ref>{{Cite journal|last1=Yuan|first1=R.-X.|last2=Bao|first2=D.|last3=Zhang|first3=Y.|date=May 2020|title=Linc00707 promotes cell proliferation, invasion, and migration via the miR-30c/CTHRC1 regulatory loop in breast cancer|url=http://doi.org/10.26355/eurrev_202005_21175|journal=European Review for Medical and Pharmacological Sciences|volume=24|issue=9|pages=4863–4872|doi=10.26355/eurrev_202005_21175|pmid=32432749|s2cid=218759508 |issn=1128-3602}}</ref> and thus promotes osteogenesis, contributes to hepatocellular carcinoma progression, promotes proliferation and metastasis, or indirectly regulates expression of proteins involved in cancer aggressiveness, respectively.

===Prader–Willi syndrome===