Non-coding RNA: Difference between revisions

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{{Hatnote|Compare [[untranslated region]]s.}}

{{short description|Class of ribonucleic acid that is not translated into proteins}}

[[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.]]

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

A '''non-coding RNA''' ('''ncRNA''') is ana functional [[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]].

[[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]]. 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 themnon-coding transcripts.<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 = 1149–541149–1154 | date = May 2005 | pmid = 15790807 | doi = 10.1126/science.1108625 | s2cid = 13047538 | 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 | titledisplay-authors = 6 | title = Demystifying emerging bulk RNA-Seq applications: the application and utility of bioinformatic methodology | journal = Briefings in Bioinformatics | volume = 22 | issue = 6 | date = NovNovember 2021 | article-number = bbab259 | 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 = 852–64852–864 | 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-lastveditors = Eddy SR | editor1doi-firstaccess = Sean R.free }}</ref>
Many of the newly identified ncRNAs have notunknown been validated forfunctions, theirif functionany.<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 = 289–97289–297 | 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 itnon-coding transcription is functional.: Somesome researchersbelieve havemost arguedncRNAs thatto many ncRNAs arebe 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 = 287–8287–288 | 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,while arguingothers insteadexpect that many ofnon-coding the current ncRNAs dotranscripts have functions and that those functions are being and will continue to be discovered.<ref>{{cite book |last1 vauthors = Mattick |first1=JohnJ, |last2=Amaral |first2=PauloP |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 vauthors = Lee |first1=HyunminH, |last2=Zhang |first2=ZhaoleiZ, |last3=Krause |first3=Henry M.HM | 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 | date = December 2019 | pmid = 31662190 | doi = 10.1016/j.tig.2019.09.006|pmid=31662190 | s2cid = 204975291 | doi-access = free }}</ref>

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

==History and discovery==

{{further|History of molecular biology}}

[[Nucleic acid]]s were first discovered in 1868 by [[Friedrich Miescher]],<ref>{{cite journal | vauthors = Dahm R | title = Friedrich Miescher and the discovery of DNA | journal = Developmental Biology | volume = 278 | issue = 2 | pages = 274–88274–288 | date = February 2005 | pmid = 15680349 | doi = 10.1016/j.ydbio.2004.11.028 }}</ref> and by 1939, RNA had been implicated in [[protein biosynthesis|protein synthesis]].<ref>{{cite journal | journal=Nature | vauthors = Caspersson T, Schultz J | title = Pentose nucleotides in the cytoplasm of growing tissues | year = 1939 | volume = 143 | doi = 10.1038/143602c0 | pages =602–3 | issue = 3623 | bibcode = 1939Natur.143..602C | s2cid = 4140563 }}</ref> Two decades later, [[Francis Crick]] predicted a functional RNA component which mediated [[translation (genetics)|translation]]; he reasoned that RNA is better suited to base-pair with an mRNA transcript than a pure [[polypeptide]].<ref>{{cite journal | vauthors = Crick FH | title = On protein synthesis | journal = Symposia of the Society for Experimental Biology | volume = 12 | pages = 138–63138–163 | year = 1958 | pmid = 13580867 }}</ref>

[[Image:TRNA-Phe yeast 1ehz.png|thumb|250px|The cloverleaf structure of Yeast tRNA^Phe (''inset'') and the 3D structure determined by X-ray analysis.]]

The first non-coding RNA to be characterised was an [[alanine]] tRNA found in [[baker's yeast]], its structure was published in 1965.<ref name="Hol65">{{cite journal | vauthors = Holley RW, Apgar J, Everett GA, Madison JT, Marquisee M, Merrill SH, Penswick JR, Zamir A | display-authors = 6 | title = Structure of a Ribonucleic Acid | journal = Science | volume = 147 | issue = 3664 | pages = 1462–51462–1465 | date = March 1965 | pmid = 14263761 | doi = 10.1126/science.147.3664.1462 | s2cid = 40989800 | bibcode = 1965Sci...147.1462H | display-authors = 1 | title = Structure of a Ribonucleic Acid | s2cid = 40989800 }}</ref> To produce a purified alanine tRNA sample, [[Robert W. Holley]] ''et al.'' used 140[[kilogram|kg]] of commercial baker's yeast to give just 1[[gram|g]] of purified tRNA^Ala for analysis.<ref name="Nobel68">{{cite web | url = http://nobelprize.org/nobel_prizes/medicine/laureates/1968/index.html | title = The Nobel Prize in Physiology or Medicine 1968 | access-date = 2007-07-28 | publisher = Nobel Foundation}}</ref> The 80 [[nucleotide]] tRNA was sequenced by first being digested with [[Pancreatic ribonuclease]] (producing fragments ending in [[Cytosine]] or [[Uridine]]) and then with takadiastase ribonuclease Tl (producing fragments which finished with [[Guanosine]]). [[Chromatography]] and identification of the 5' and 3' ends then helped arrange the fragments to establish the RNA sequence.<ref name="Nobel68" /> Of the three structures originally proposed for this tRNA,<ref name="Hol65" /> the 'cloverleaf' structure was independently proposed in several following publications.<ref name="pmid5938777">{{cite journal | vauthors = Madison JT, Everett GA, Kung H | title = Nucleotide sequence of a yeast tyrosine transfer RNA | journal = Science | volume = 153 | issue = 3735 | pages = 531–4531–534 | date = July 1966 | pmid = 5938777 | doi = 10.1126/science.153.3735.531 | bibcodes2cid = 1966Sci...153..531M9265016 | citeseerx = 10.1.1.1001.2662 | s2cidbibcode = 92650161966Sci...153..531M }}</ref><ref>{{cite journal | vauthors = Zachau HG, Dütting D, Feldmann H, Melchers F, Karau W | title = Serine specific transfer ribonucleic acids. XIV. Comparison of nucleotide sequences and secondary structure models | journal = Cold Spring Harbor Symposia on Quantitative Biology | volume = 31 | pages = 417–24417–424 | year = 1966 | pmid = 5237198 | doi = 10.1101/SQB.1966.031.01.054 }}</ref><ref>{{cite journal | vauthors = Dudock BS, Katz G, Taylor EK, Holley RW | title = Primary structure of wheat germ phenylalanine transfer RNA | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 62 | issue = 3 | pages = 941–5941–945 | date = March 1969 | pmid = 5257014 | pmc = 223689 | doi = 10.1073/pnas.62.3.941 | doi-access = free | bibcode = 1969PNAS...62..941D | doi-access = free }}</ref><ref>{{cite journal | vauthors = Cramer F, Doepner H, Haar F VD, Schlimme E, Seidel H | title = On the conformation of transfer RNA | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 61 | issue = 4 | pages = 1384–911384–1391 | date = December 1968 | pmid = 4884685 | pmc = 225267 | doi = 10.1073/pnas.61.4.1384 | doi-access = free | bibcode = 1968PNAS...61.1384C | doi-access = free }}</ref> The cloverleaf [[secondary structure]] was finalised following [[X-ray crystallography]] analysis performed by two independent research groups in 1974.<ref>{{cite journal | vauthors = Ladner JE, Jack A, Robertus JD, Brown RS, Rhodes D, Clark BF, Klug A | title = Structure of yeast phenylalanine transfer RNA at 2.5 A resolution | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 72 | issue = 11 | pages = 4414–84414–4418 | date = November 1975 | pmid = 1105583 | pmc = 388732 | doi = 10.1073/pnas.72.11.4414 | doi-access = free | bibcode = 1975PNAS...72.4414L | display-authors = 1 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Kim SH, Quigley GJ, Suddath FL, McPherson A, Sneden D, Kim JJ, Weinzierl J, Rich A | display-authors = 6 | title = Three-dimensional structure of yeast phenylalanine transfer RNA: folding of the polynucleotide chain | journal = Science | volume = 179 | issue = 4070 | pages = 285–8285–288 | date = January 1973 | pmid = 4566654 | doi = 10.1126/science.179.4070.285 | s2cid = 28916938 | bibcode = 1973Sci...179..285K | s2cid = 28916938 | display-authors = 1 }}</ref>

[[Ribosomal RNA]] was next to be discovered, followed by URNA in the early 1980s. Since then, the discovery of new non-coding RNAs has continued with [[snoRNAs]], [[Xist]], [[CRISPR]] and many more.<ref name="Edd01">{{cite journal | vauthors = Eddy SR | title = Non-coding RNA genes and the modern RNA world | journal = Nature Reviews. Genetics | volume = 2 | issue = 12 | pages = 919–29919–929 | date = December 2001 | pmid = 11733745 | doi = 10.1038/35103511 | s2cid = 18347629 }}</ref> Recent notable additions include [[riboswitch]]es and [[miRNA]]; the discovery of the RNAi [[mechanism (biology)|mechanism]] associated with the latter earned [[Craig C. Mello]] and [[Andrew Fire]] the 2006 [[Nobel Prize in Physiology or Medicine]].<ref>{{cite web | title=Advanced Information: RNA interference | lastvauthors = Daneholt | first=BertilB | work=The Nobel Prize in Physiology or Medicine 2006 | url=http://nobelprize.org/nobel_prizes/medicine/laureates/2006/adv.html | access-date=2007-01-25 | archive-url=https://web.archive.org/web/20070120113455/http://nobelprize.org/nobel_prizes/medicine/laureates/2006/adv.html <!--Added by H3llBot--> | archive-date=2007-01-20}}</ref>

Recent discoveries of ncRNAs have been achieved through both experimental and [[Bioinformatics discovery of non-coding RNAs|bioinformatic methods]].

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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 | doipmc = 10.2174/13892029206661911291127057327968 | pmcdoi = 732796810.2174/1389202920666191129112705 }}</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 fossilsfossil]]s 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 | s2cid = 2029318 | 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 | s2cid = 17968659 | 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 = 880–9880–889 | 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>

[[Image:010 large subunit-1FFK.gif|thumb|left|Atomic structure of the 50S Subunit from ''[[Haloarcula|''Haloarcula marismortui]]'']]. Proteins are shown in blue and the two RNA strands in orange and yellow.<ref name=Ban>{{cite journal | vauthors = Ban N, Nissen P, Hansen J, Moore PB, Steitz TA | title = The complete atomic structure of the large ribosomal subunit at 2.4 A resolution | journal = Science | volume = 289 | issue = 5481 | pages = 905–20905–920 | date = August 2000 | pmid = 10937989 | doi = 10.1126/science.289.5481.905 | bibcodeciteseerx = 2000Sci10.1.1.28958..905B2271 | citeseerxbibcode = 102000Sci.1.1.58289.2271.905B }}</ref> The small patch of green in the center of the subunit is the active site.]]

===In translation===

[[Image:010 large subunit-1FFK.gif|thumb|left|Atomic structure of the 50S Subunit from ''[[Haloarcula|Haloarcula marismortui]]''. Proteins are shown in blue and the two RNA strands in orange and yellow.<ref name=Ban>{{cite journal | vauthors = Ban N, Nissen P, Hansen J, Moore PB, Steitz TA | title = The complete atomic structure of the large ribosomal subunit at 2.4 A resolution | journal = Science | volume = 289 | issue = 5481 | pages = 905–20 | date = August 2000 | pmid = 10937989 | doi = 10.1126/science.289.5481.905 | bibcode = 2000Sci...289..905B | citeseerx = 10.1.1.58.2271 }}</ref> The small patch of green in the center of the subunit is the active site.]]

Many of the conserved, essential and abundant ncRNAs are involved in [[Translation (genetics)|translation]]. [[Ribonucleoprotein]] (RNP) particles called [[ribosome]]s are the 'factories' where translation takes place in the cell. The ribosome consists of more than 60% [[rRNA|ribosomal RNA]]; these are made up of 3 ncRNAs in [[prokaryotes]] and 4 ncRNAs in [[eukaryotes]]. Ribosomal RNAs catalyse the translation of nucleotide sequences to protein. Another set of ncRNAs, [[Transfer RNA]]s, form an 'adaptor molecule' between [[mRNA]] and protein. The [[snoRNA|H/ACA box and C/D box snoRNAs]] are ncRNAs found in archaea and eukaryotes. [[RNase MRP]] is restricted to eukaryotes. Both groups of ncRNA are involved in the maturation of rRNA. The snoRNAs guide covalent modifications of rRNA, tRNA and [[snRNA]]s; RNase MRP cleaves the [[internal transcribed spacer 1]] between 18S and 5.8S rRNAs. The ubiquitous ncRNA, [[RNase P]], is an evolutionary relative of RNase MRP.<ref name="PMID16540690">{{cite journal | vauthors = Zhu Y, Stribinskis V, Ramos KS, Li Y | title = Sequence analysis of RNase MRP RNA reveals its origination from eukaryotic RNase P RNA | journal = RNA | volume = 12 | issue = 5 | pages = 699–706 | date = May 2006 | pmid = 16540690 | pmc = 1440897 | doi = 10.1261/rna.2284906 }}</ref> RNase P matures tRNA sequences by generating mature 5'-ends of tRNAs through cleaving the 5'-leader elements of precursor-tRNAs. Another ubiquitous RNP called [[Signal recognition particle|SRP]] recognizes and transports specific nascent proteins to the [[endoplasmic reticulum]] in [[eukaryote]]s and the [[plasma membrane]] in [[prokaryote]]s. In bacteria, [[tmRNA|Transfer-messenger RNA]] (tmRNA) is an RNP involved in rescuing stalled ribosomes, tagging incomplete [[Peptide|polypeptides]] and promoting the degradation of aberrant mRNA.{{citation needed|date=June 2017}}

===In RNA splicing===

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[[File:Yeast tri-snRNP.jpg|thumb|left|Electron microscopy images of the yeast spliceosome. Note the bulk of the complex is in fact ncRNA.]]

In eukaryotes, the [[spliceosome]] performs the [[RNA splicing|splicing]] reactions essential for removing [[intron]] sequences, this process is required for the formation of mature [[mRNA]]. The [[spliceosome]] is another RNP often also known as the [[snRNP]] or tri-snRNP. There are two different forms of the spliceosome, the major and minor forms. The ncRNA components of the major spliceosome are [[U1 snRNA|U1]], [[U2 snRNA|U2]], [[U4 snRNA|U4]], [[U5 snRNA|U5]], and [[U6 snRNA|U6]]. The ncRNA components of the minor spliceosome are [[U11 snRNA|U11]], [[U12 snRNA|U12]], [[U5 snRNA|U5]], [[U4atac minor spliceosomal RNA|U4atac]] and [[U6atac minor spliceosomal RNA|U6atac]].{{citation needed|date=June 2017}}

Another group of introns can catalyse their own removal from host transcripts; these are called self-splicing RNAs. There are two main groups of self-splicing RNAs: [[group I catalytic intron]] and [[group II catalytic intron]]. These ncRNAs catalyze their own excision from mRNA, tRNA and rRNA precursors in a wide range of organisms.{{citation needed|date=June 2017}}

In mammals it has been found that snoRNAs can also regulate the [[alternative splicing]] of mRNA, for example snoRNA [[Small nucleolar RNA SNORD115|HBII-52]] regulates the splicing of [[5-HT2C receptor|serotonin receptor 2C]].<ref name=Kishore>{{cite journal | vauthors = Kishore S, Stamm S | title = The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C | journal = Science | volume = 311 | issue = 5758 | pages = 230–2230–232 | date = January 2006 | pmid = 16357227 | doi = 10.1126/science.1118265 | s2cid = 44527461 | doi-access = free | bibcode = 2006Sci...311..230K | s2cid = 44527461 }}</ref>

In nematodes, the [[SmY]] ncRNA appears to be involved in mRNA [[trans-splicing]].<ref>{{citationCite journal |last1=Jones |first1=Thomas A. |last2=Otto |first2=Wolfgang |last3=Marz |first3=Manja |last4=Eddy |first4=Sean R. |last5=Stadler |first5=Peter F. needed|date=June2009 2017|title=A survey of nematode SmY RNAs |journal=RNA Biology |volume=6 |issue=1 |pages=5–8 |doi=10.4161/rna.6.1.7634 |issn=1555-8584 |pmid=19106623}}</ref>

===In DNA replication===

[[File:YRNA-Ro60.png|thumb|250px|The [[TRIM21|Ro autoantigen]] protein (white) binds the end of a double-stranded Y RNA (red) and a single stranded RNA (blue). (PDB: 1YVP [http://www.rcsb.org/pdb/explore.do?structureId=1yvp]).<ref name="pmid15907467">{{cite journal | vauthors = Stein AJ, Fuchs G, Fu C, Wolin SL, Reinisch KM | title = Structural insights into RNA quality control: the Ro autoantigen binds misfolded RNAs via its central cavity | journal = Cell | volume = 121 | issue = 4 | pages = 529–39529–539 | date = May 2005 | pmid = 15907467 | pmc = 1769319 | doi = 10.1016/j.cell.2005.03.009 }}</ref>]]

[[Y RNA]]s are stem loops, necessary for [[DNA replication]] through interactions with [[chromatin]] and initiation proteins (including the [[origin recognition complex]]).<ref name="pmid16943439">{{cite journal | vauthors = Christov CP, Gardiner TJ, Szüts D, Krude T | title = Functional requirement of noncoding Y RNAs for human chromosomal DNA replication | journal = Molecular and Cellular Biology | volume = 26 | issue = 18 | pages = 6993–7004 | date = September 2006 | pmid = 16943439 | pmc = 1592862 | doi = 10.1128/MCB.01060-06 }}</ref><ref>{{cite journal | vauthors = Zhang AT, Langley AR, Christov CP, Kheir E, Shafee T, Gardiner TJ, Krude T | title = Dynamic interaction of Y RNAs with chromatin and initiation proteins during human DNA replication | journal = Journal of Cell Science | volume = 124 | issue = Pt 12 | pages = 2058–692058–2069 | date = June 2011 | pmid = 21610089 | pmc = 3104036 | doi = 10.1242/jcs.086561 }}</ref> They are also components of the [[TRIM21|Ro60 ribonucleoprotein particle]]<ref>{{cite journal | vauthors = Hall AE, Turnbull C, Dalmay T | title = Y RNAs: recent developments | journal = Biomolecular Concepts | volume = 4 | issue = 2 | pages = 103–10103–110 | date = April 2013 | pmid = 25436569 | doi = 10.1515/bmc-2012-0050 | s2cid = 12575326 | doi-access = free }}</ref> which is a target of autoimmune antibodies in patients with [[systemic lupus erythematosus]].<ref>{{cite journal | vauthors = Lerner MR, Boyle JA, Hardin JA, Steitz JA | title = Two novel classes of small ribonucleoproteins detected by antibodies associated with lupus erythematosus | journal = Science | volume = 211 | issue = 4480 | pages = 400–2400–402 | date = January 1981 | pmid = 6164096 | doi = 10.1126/science.6164096 | bibcode = 1981Sci...211..400L }}</ref>

===In gene regulation===

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====Trans-acting====

In higher eukaryotes [[microRNA]]s regulate gene expression. A single miRNA can reduce the expression levels of hundreds of genes. The mechanism by which mature miRNA molecules act is through partial complementarycomplementarity to one or more messenger RNA (mRNA) molecules, generally in [[Three prime untranslated region|3' UTRs]]. The main function of miRNAs is to down-regulate gene expression.

The ncRNA [[RNase P]] has also been shown to influence gene expression. In the human nucleus, [[RNase P]] is required for the normal and efficient transcription of various ncRNAs transcribed by [[RNA polymerase III]]. These include tRNA, [[5S ribosomal RNA|5S rRNA]], [[Signal recognition particle|SRP]] RNA, and [[U6 spliceosomal RNA|U6 snRNA]] genes. RNase P exerts its role in transcription through association with Pol III and [[chromatin]] of active tRNA and 5S rRNA genes.<ref name="pmid16778078">{{cite journal | vauthors = Reiner R, Ben-Asouli Y, Krilovetzky I, Jarrous N | title = A role for the catalytic ribonucleoprotein RNase P in RNA polymerase III transcription | journal = Genes & Development | volume = 20 | issue = 12 | pages = 1621–351621–1635 | date = June 2006 | pmid = 16778078 | pmc = 1482482 | doi = 10.1101/gad.386706 }}</ref>

It has been shown that [[7SK RNA]], a [[metazoan]] ncRNA, acts as a negative regulator of the [[RNA polymerase II]] [[elongation factor|elongation factor P-TEFb]], and that this activity is influenced by stress response pathways.{{citation needed|date=June 2017}}

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The bacterial ncRNA, [[6S RNA]], specifically associates with RNA polymerase holoenzyme containing the [[Sigma factor|sigma70]] specificity factor. This interaction represses expression from a sigma70-dependent [[promoter (biology)|promoter]] during [[Bacterial growth|stationary phase]].{{citation needed|date=June 2017}}

Another bacterial ncRNA, [[OxyS RNA]] represses translation by binding to [[Shine-Dalgarno sequencessequence]]s thereby occluding ribosome binding. OxyS RNA is induced in response to oxidative stress in Escherichia coli.{{citation needed|date=June 2017}}

The B2 RNA is a small noncoding RNA polymerase III transcript that represses mRNA transcription in response to heat shock in mouse

cells. B2 RNA inhibits transcription by binding to core Pol II. Through this interaction, B2 RNA assembles into preinitiation

complexes at the promoter and blocks RNA synthesis.<ref name="pmid15300239">{{cite journal | vauthors = Espinoza CA, Allen TA, Hieb AR, Kugel JF, Goodrich JA | title = B2 RNA binds directly to RNA polymerase II to repress transcript synthesis | journal = Nature Structural & Molecular Biology | volume = 11 | issue = 9 | pages = 822–9822–829 | date = September 2004 | pmid = 15300239 | doi = 10.1038/nsmb812 | s2cid = 22199826 }}</ref>

A recent study has shown that just the act of transcription of ncRNA sequence can have an influence on gene expression. [[RNA polymerase II]] transcription of ncRNAs is required for [[chromatin]] remodelling in the [[Schizosaccharomyces pombe]]. Chromatin is progressively converted to an open configuration, as several species of ncRNAs are transcribed.<ref name="pmid18820678">{{cite journal | vauthors = Hirota K, Miyoshi T, Kugou K, Hoffman CS, Shibata T, Ohta K | title = Stepwise chromatin remodelling by a cascade of transcription initiation of non-coding RNAs | journal = Nature | volume = 456 | issue = 7218 | pages = 130–4130–134 | date = November 2008 | pmid = 18820678 | doi = 10.1038/nature07348 | s2cid = 4416402 | bibcode = 2008Natur.456..130H | s2cid = 4416402 }}</ref>

====Cis-acting====

Line 84 ⟶ 83:

[[Piwi-interacting RNA]]s (piRNAs) expressed in

[[mammal]]ian [[testes]] and [[somatic cell]]s form RNA-protein complexes with [[Piwi]] proteins. These piRNA complexes (piRCs) have been linked to transcriptional gene silencing of [[retrotransposon]]s and other genetic elements in [[germ linegermline]] cells, particularly those in [[spermatogenesis]].

[[CRISPR|Clustered Regularly Interspaced Short Palindromic Repeats]] (CRISPR) are repeats found in the [[DNA]] of many [[bacteria]] and [[archaea]]. The repeats are separated by spacers of similar length. It has been demonstrated that these spacers can be derived from phage and subsequently help protect the cell from infection.

Line 92 ⟶ 91:

[[Telomerase]] is an RNP [[enzyme]] that adds specific [[DNA]] sequence repeats ("TTAGGG" in vertebrates) to [[telomere|telomeric]] regions, which are found at the ends of eukaryotic [[chromosomes]]. The telomeres contain condensed DNA material, giving stability to the chromosomes. The enzyme is a [[reverse transcriptase]] that carries [[Vertebrate telomerase RNA|Telomerase RNA]], which is used as a template when it elongates telomeres, which are shortened after each [[cell cycle|replication cycle]].

[[Xist]] (X-inactive-specific transcript) is a long ncRNA gene on the [[X chromosome]] of the [[Eutheria|placental mammals]] that acts as major effector of the [[X inactivation|X chromosome inactivation]] process forming [[Barr body|Barr bodies]]. An [[antisense RNA]], [[X-inactivation#Xist and Tsix RNAs|Tsix]], is a negative regulator of Xist. X chromosomes lacking Tsix expression (and thus having high levels of Xist transcription) are inactivated more frequently than normal chromosomes. In [[drosophila|drosophilids]], which also use an [[XY sex-determination system]], the [[Drosophila roX RNA|roX]] (RNA on the X) RNAs are involved in dosage compensation.<ref name="pmid12446910">{{cite journal | vauthors = Park Y, Kelley RL, Oh H, Kuroda MI, Meller VH | title = Extent of chromatin spreading determined by roX RNA recruitment of MSL proteins | journal = Science | volume = 298 | issue = 5598 | pages = 1620–31620–1623 | date = November 2002 | pmid = 12446910 | doi = 10.1126/science.1076686 | s2cid = 27167367 | bibcode = 2002Sci...298.1620P | s2cid = 27167367 }}</ref> Both Xist and roX operate by [[epigenetics|epigenetic]] regulation of transcription through the recruitment of [[Histone-Modifying Enzymes|histone-modifying enzymes]].

===Bifunctional RNA===

''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 = 20454–920454–20459 | date = December 2007 | pmid = 18042713 | pmc = 2154452 | doi = 10.1073/pnas.0708102104 | bibcodedoi-access = 2007PNAS..10420454Wfree | doi-accessbibcode = free2007PNAS..10420454W }}</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-lastveditors = McEntyre J | bibcodedoi-access = 2008PLSCB...4E0176Dfree | editor1-firstbibcode = Johanna2008PLSCB...4E0176D }}</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-lastveditors = Goldberg DE | editor1doi-firstaccess = Daniel Eliotfree }}</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 | display-authors = 6 | title = A human snoRNA with microRNA-like functions | journal = Molecular Cell | volume = 32 | issue = 4 | pages = 519–28519–528 | date = November 2008 | pmid = 19026782 | doi = 10.1016/j.molcel.2008.10.017 | doi-access = free }}</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 | article-number = nrs.05006 | 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 = 4119–294119–4129 | date = December 1996 | pmid = 9012531 | 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 = 3445–573445–3457 | 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 | display-authors = 6 | title = A translation-independent role of oskar RNA in early Drosophila oogenesis | journal = Development | volume = 133 | issue = 15 | pages = 2827–332827–2833 | 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 = 3144–523144–3152 | 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 | display-authors = 6 | title = P53 mRNA controls p53 activity by managing Mdm2 functions | journal = Nature Cell Biology | volume = 10 | issue = 9 | pages = 1098–1051098–1105 | 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 = 11659–7211659–11672 | date = December 2012 | pmid = 23034808 | pmc = 3526287 | doi = 10.1093/nar/gks895 }}</ref> and Bifunctional[[Spot RNAs42 haveRNA]].<ref recentlyname="pmid35239441">{{cite beenjournal | vauthors = Aoyama JJ, Raina M, Zhong A, Storz G | title = Dual-function Spot 42 RNA encodes a 15-amino acid protein that regulates the CRP transcription factor | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 119 | issue = 10 | article-number = e2119866119 | date = March 2022 | pmid = 35239441 | pmc = 8916003 | doi = 10.1073/pnas.2119866119 | doi-access = free | bibcode = 2022PNAS..11919866A }}</ref>) Bifunctional RNAs were the subject of a 2011 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–viivi-vii | date = November 2011 | pmid = 21963143 | doi = 10.1016/S0300-9084(11)00322-1 | url = https://zenodo.org/record/889579 }}</ref>

=== As a hormone ===

There is an important link between certain non-coding RNAs and the control of hormone-regulated pathways. In ''[[Drosophila]]'', hormones such as [[ecdysone]] and [[juvenile hormone]] can promote the expression of certain miRNAs. Furthermore, this regulation occurs at distinct temporal points within ''Caenorhabditis elegans'' development.<ref>{{cite journal | vauthors = Sempere LF, Sokol NS, Dubrovsky EB, Berger EM, Ambros V | title = Temporal regulation of microRNA expression in Drosophila melanogaster mediated by hormonal signals and broad-Complex gene activity | journal = Developmental Biology | volume = 259 | issue = 1 | pages = 9–18 | date = July 2003 | pmid = 12812784 | doi = 10.1016/S0012-1606(03)00208-2 | s2cid = 17249847 | doi-access = free }}</ref> In mammals, [[Mir-206|miR-206]] is a crucial regulator of [[estrogen]]-receptor-alpha.<ref>{{cite journal | vauthors = Adams BD, Furneaux H, White BA | title = The micro-ribonucleic acid (miRNA) miR-206 targets the human estrogen receptor-alpha (ERalpha) and represses ERalpha messenger RNA and protein expression in breast cancer cell lines | journal = Molecular Endocrinology | volume = 21 | issue = 5 | pages = 1132–471132–1147 | date = May 2007 | pmid = 17312270 | doi = 10.1210/me.2007-0022 | doi-access = free }}</ref>

Non-coding RNAs are crucial in the development of several endocrine organs, as well as in endocrine diseases such as [[diabetes mellitus]].<ref>{{cite journal | vauthors = Knoll M, Lodish HF, Sun L | title = Long non-coding RNAs as regulators of the endocrine system | journal = Nature Reviews. Endocrinology | volume = 11 | issue = 3 | pages = 151–60151–160 | date = March 2015 | pmid = 25560704 | pmc = 4376378 | doi = 10.1038/nrendo.2014.229 | hdl = 1721.1/116703 }}</ref> Specifically in the MCF-7 cell line, addition of 17β-[[estradiol]] increased global transcription of the noncoding RNAs called [[long noncoding RNA]]s (lncRNAs) near estrogen-activated coding genes.<ref>{{cite journal | vauthors = Li W, Notani D, Ma Q, Tanasa B, Nunez E, Chen AY, Merkurjev D, Zhang J, Ohgi K, Song X, Oh S, Kim HS, Glass CK, Rosenfeld MG | display-authors = 6 | title = Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation | journal = Nature | volume = 498 | issue = 7455 | pages = 516–20516–520 | date = June 2013 | pmid = 23728302 | pmc = 3718886 | doi = 10.1038/nature12210 | bibcode = 2013Natur.498..516L }}</ref>

===In pathogenic avoidance===

''[[C. elegans]]'' was shown to learn and inherit [[Poison shyness|pathogenic]] [[Avoidance response|avoidance]] after exposure to a single non-coding RNA of a [[Pathogenic bacteria|bacterial pathogen]].<ref>{{cite news |title=Researchers discover how worms pass knowledge of a pathogen to offspring |url=https://phys.org/news/2020-09-worms-knowledge-pathogen-offspring.html |access-date=11 October 2020 |work=phys.org |language=en}}</ref><ref>{{cite journal |last1 vauthors = Kaletsky |first1=RachelR, |last2=Moore |first2=RebeccaRS, S. |last3=Vrla |first3=GeoffreyGD, D. |last4=Parsons |first4=LanceLR, R. |last5=Gitai |first5=ZemerZ, |last6=Murphy CT |first6=Coleen T.title |title= C. elegans interprets bacterial non-coding RNAs to learn pathogenic avoidance | journal = Nature |date=9 September 2020 |volume = 586 | issue = 7829 | pages = 445–451 | date = October 2020 | pmid = 32908307 | pmc = 8547118 | doi = 10.1038/s41586-020-2699-5 |pmc s2cid =8547118 221626129 |pmid=32908307 |bibcode = 2020Natur.586..445K |s2cid=221626129 |language=en |issn=1476-4687}}</ref>

==Roles in disease==

Line 118 ⟶ 117:

===Cancer===

Many ncRNAs show abnormal expression patterns in [[cancer]]ous tissues.<ref name="Shahrouki P 2012"/> These include [[microRNA|miRNAs]], [[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 = 135–41135–141 | 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 = 447–54447–454 | 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 = 981–8981–988 | 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 | display-authors = 6 | title = The widespread impact of mammalian MicroRNAs on mRNA repression and evolution | journal = Science | volume = 310 | issue = 5755 | pages = 1817–211817–1821 | date = December 2005 | pmid = 16308420 | doi = 10.1126/science.1121158 | s2cid = 1849875 | 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 | display-authors = 6 | title = Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs | journal = Nature | volume = 433 | issue = 7027 | pages = 769–73769–773 | date = February 2005 | pmid = 15685193 | doi = 10.1038/nature03315 | s2cid = 4430576 | 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]]{{Broken anchor|date=2025-05-23|bot=User:Cewbot/log/20201008/configuration|target_link=Telomere#Human telomeres.2C cancer.2C and ALT.|reason= }} for more information). The direct function of the long mRNA-like ncRNAs is less clear.

[[Germ-lineGermline]] 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 | display-authors = 6 | 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 = 1793–8011793–1801 | date = October 2005 | pmid = 16251535 | doi = 10.1056/NEJMoa050995 | doi-access = free }}</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 | display-authors = 6 | 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 = 15524–915524–15529 | date = November 2002 | pmid = 12434020 | pmc = 137750 | doi = 10.1073/pnas.242606799 | bibcodedoi-access = 2002PNAS...9915524Cfree | doi-accessbibcode = free2002PNAS...9915524C }}</ref>

It has been suggested that a rare [[Single-nucleotide polymorphism|SNP]] ([[rs11614913]]) that overlaps [[Mir-196 microRNA precursor family|hsa-mir-196a-2]] has been found to be associated with [[non-small cell lung carcinoma]].<ref name="pmid18521189">{{cite journal | vauthors = Hu Z, Chen J, Tian T, Zhou X, Gu H, Xu L, Zeng Y, Miao R, Jin G, Ma H, Chen Y, Shen H | display-authors = 6 | title = Genetic variants of miRNA sequences and non-small cell lung cancer survival | journal = The Journal of Clinical Investigation | volume = 118 | issue = 7 | pages = 2600–82600–2608 | date = July 2008 | pmid = 18521189 | pmc = 2402113 | doi = 10.1172/JCI34934 }}</ref> Likewise, a screen of 17 miRNAs that have been predicted to regulate a number of breast cancer associated genes found variations in the microRNAs [[Mir-17 microRNA precursor family|miR-17]] and [[Mir-30 microRNA precursor|miR-30c-1]]of patients; these patients were noncarriers of [[BRCA1]] or [[BRCA2]] mutations, lending the possibility that familial breast cancer may be caused by variation in these miRNAs.<ref name="pmid19048628">{{cite journal | vauthors = Shen J, Ambrosone CB, Zhao H | title = Novel genetic variants in microRNA genes and familial breast cancer | journal = International Journal of Cancer | volume = 124 | issue = 5 | pages = 1178–821178–1182 | date = March 2009 | pmid = 19048628 | doi = 10.1002/ijc.24008 | s2cid = 20960029 | doi-access = free }}</ref>

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>{{Citecite journal |last1 vauthors = Jia|first1=Bo|last2= B, Wang|first2=Zhiping|last3= Z, Sun|first3=Xiang|last4= X, Chen|first4=Jun|last5= J, Zhao|first5=Jianjiang|last6= J, Qiu X |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 article-019-1161-9|issnnumber =1757-6512|pmc=6387535|pmid=30795799}}</ref> in67 hepatocellular| carcinoma,<ref>{{Citedate 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 February 2019 |title=LINC00707 contributespmid to= hepatocellular30795799 carcinoma| progressionpmc via= sponging6387535 miR‐206| todoi increase= CDK14|url=https://onlinelibrary.wiley.com/doi/abs/10.10021186/jcp.27737s13287-019-1161-9 |journal doi-access =Journal offree 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>{{Citecite journal |last1 vauthors = Xie|first1=Min|last2= M, Ma|first2=Tianshi|last3= T, Xue|first3=Jiangyang|last4= J, Ma|first4=Hongwei|last5= H, Sun|first5=Ming|last6= M, Zhang|first6=Zhihong|last7= Z, Liu|first7=Minjuan|last8= M, Liu|first8=Yinghua|last9= Y, Ju|first9=Songwen|last10= S, Wang|first10=Zhaoxia|last11= Z, De W |first11 display-authors =Wei|date=February 20196 | 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 | date = February 2019 | pmid = 30502359 | doi = 10.1016/j.canlet.2018.11.032 |pmid=30502359| s2cid = 54611497 }}</ref> or breast cancer,<ref>{{Citecite journal |last1 vauthors = Li|first1=Tong|last2= T, Li|first2=Yunpeng|last3= Y, Sun H |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 date =en 2019-06-06 | pmid = 31239777 | pmc = 6559252 | doi = 10.2147/cmar.s210845 |pmc doi-access =6559252|pmid=31239777 free }}</ref><ref>{{Citecite journal |last1 vauthors = Yuan|first1=R.-X.|last2= RX, 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 | date = May 2020 | pmid = 32432749 | 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===

The deletion of the 48 copies of the C/D box snoRNA [[Small nucleolar RNA SNORD116|SNORD116]] has been shown to be the primary cause of [[Prader&ndash;Willi syndrome]].<ref name="pmid18500341">{{cite journal | vauthors = Sahoo T, del Gaudio D, German JR, Shinawi M, Peters SU, Person RE, Garnica A, Cheung SW, Beaudet AL | display-authors = 6 | title = Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster | journal = Nature Genetics | volume = 40 | issue = 6 | pages = 719–21719–721 | date = June 2008 | pmid = 18500341 | pmc = 2705197 | doi = 10.1038/ng.158 }}</ref><ref name="pmid18166085">{{cite journal | vauthors = Skryabin BV, Gubar LV, Seeger B, Pfeiffer J, Handel S, Robeck T, Karpova E, Rozhdestvensky TS, Brosius J | display-authors = 6 | title = Deletion of the MBII-85 snoRNA gene cluster in mice results in postnatal growth retardation | journal = PLOS Genetics | volume = 3 | issue = 12 | pages = e235 | date = December 2007 | pmid = 18166085 | pmc = 2323313 | doi = 10.1371/journal.pgen.0030235 | doi-access = free }}</ref><ref name="pmid18320030">{{cite journal | vauthors = Ding F, Li HH, Zhang S, Solomon NM, Camper SA, Cohen P, Francke U | title = SnoRNA Snord116 (Pwcr1/MBII-85) deletion causes growth deficiency and hyperphagia in mice | journal = PLOS ONE | volume = 3 | issue = 3 | pages = e1709 | date = March 2008 | pmid = 18320030 | pmc = 2248623 | doi = 10.1371/journal.pone.0001709 | editor1-lastveditors = Akbarian S | doi-access = free | bibcode = 2008PLoSO...3.1709D | editor1-first = Schahram | doi-access = free }}</ref><ref name="pmid16075369">{{cite journal | vauthors = Ding F, Prints Y, Dhar MS, Johnson DK, Garnacho-Montero C, Nicholls RD, Francke U | title = Lack of Pwcr1/MBII-85 snoRNA is critical for neonatal lethality in Prader-Willi syndrome mouse models | journal = Mammalian Genome | volume = 16 | issue = 6 | pages = 424–31424–431 | date = June 2005 | pmid = 16075369 | doi = 10.1007/s00335-005-2460-2 | s2cid = 12256515 }}</ref> Prader–Willi is a developmental disorder associated with over-eating and learning difficulties. SNORD116 has potential target sites within a number of protein-coding genes, and could have a role in regulating alternative splicing.<ref name="pmid18160232">{{cite journal | vauthors = Bazeley PS, Shepelev V, Talebizadeh Z, Butler MG, Fedorova L, Filatov V, Fedorov A | title = snoTARGET shows that human orphan snoRNA targets locate close to alternative splice junctions | journal = Gene | volume = 408 | issue = 1–2 | pages = 172–9172–179 | date = January 2008 | pmid = 18160232 | pmc = 6800007 | doi = 10.1016/j.gene.2007.10.037 }}</ref>

===Autism===

The chromosomal locus containing the [[small nucleolar RNA SNORD115]] gene cluster has been duplicated in approximately 5% of individuals with [[autism|autistic traits]].<ref name="pmid15318025">{{cite journal | vauthors = Bolton PF, Veltman MW, Weisblatt E, Holmes JR, Thomas NS, Youings SA, Thompson RJ, Roberts SE, Dennis NR, Browne CE, Goodson S, Moore V, Brown J | display-authors = 6 | title = Chromosome 15q11-13 abnormalities and other medical conditions in individuals with autism spectrum disorders | journal = Psychiatric Genetics | volume = 14 | issue = 3 | pages = 131–7131–137 | date = September 2004 | pmid = 15318025 | doi = 10.1097/00041444-200409000-00002 | s2cid = 37344935 }}</ref><ref name="pmid18923514">{{cite journal | vauthors = Cook EH, Scherer SW | title = Copy-number variations associated with neuropsychiatric conditions | journal = Nature | volume = 455 | issue = 7215 | pages = 919–23919–923 | date = October 2008 | pmid = 18923514 | doi = 10.1038/nature07458 | s2cid = 4377899 | bibcode = 2008Natur.455..919C | s2cid = 4377899 }}</ref> A mouse model engineered to have a duplication of the SNORD115 cluster displays autistic-like behaviour.<ref name="pmid19563756">{{cite journal | vauthors = Nakatani J, Tamada K, Hatanaka F, Ise S, Ohta H, Inoue K, Tomonaga S, Watanabe Y, Chung YJ, Banerjee R, Iwamoto K, Kato T, Okazawa M, Yamauchi K, Tanda K, Takao K, Miyakawa T, Bradley A, Takumi T | display-authors = 6 | title = Abnormal behavior in a chromosome-engineered mouse model for human 15q11-13 duplication seen in autism | journal = Cell | volume = 137 | issue = 7 | pages = 1235–461235–1246 | date = June 2009 | pmid = 19563756 | pmc = 3710970 | doi = 10.1016/j.cell.2009.04.024 }}</ref> A recent small study of post-mortem brain tissue demonstrated altered expression of long non-coding RNAs in the prefrontal cortex and cerebellum of autistic brains as compared to controls.<ref>{{cite journal | vauthors = Ziats MN, Rennert OM | title = Aberrant expression of long noncoding RNAs in autistic brain | journal = Journal of Molecular Neuroscience | volume = 49 | issue = 3 | pages = 589–93589–593 | date = March 2013 | pmid = 22949041 | pmc = 3566384 | doi = 10.1007/s12031-012-9880-8 }}</ref>

===Cartilage–hair hypoplasia===

Mutations within [[RNase MRP]] have been shown to cause [[cartilage–hair hypoplasia]], a disease associated with an array of symptoms such as short stature, sparse hair, skeletal abnormalities and a suppressed immune system that is frequent among [[Amish]] and [[Finland|Finnish]].<ref name="pmid11207361">{{cite journal | vauthors = Ridanpää M, van Eenennaam H, Pelin K, Chadwick R, Johnson C, Yuan B, vanVenrooij W, Pruijn G, Salmela R, Rockas S, Mäkitie O, Kaitila I, de la Chapelle A | display-authors = 6 | title = Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia | journal = Cell | volume = 104 | issue = 2 | pages = 195–203 | date = January 2001 | pmid = 11207361 | doi = 10.1016/S0092-8674(01)00205-7 | s2cid = 13977736 | doi-access = free | hdl = 2066/185709 | hdl-access = free }}</ref><ref name="pmid17189938">{{cite journal | vauthors = Martin AN, Li Y | title = RNase MRP RNA and human genetic diseases | journal = Cell Research | volume = 17 | issue = 3 | pages = 219–26219–226 | date = March 2007 | pmid = 17189938 | doi = 10.1038/sj.cr.7310120 | doi-access = free }}</ref><ref name="pmid18804272">{{cite journal | vauthors = Kavadas FD, Giliani S, Gu Y, Mazzolari E, Bates A, Pegoiani E, Roifman CM, Notarangelo LD | display-authors = 6 | title = Variability of clinical and laboratory features among patients with ribonuclease mitochondrial RNA processing endoribonuclease gene mutations | journal = The Journal of Allergy and Clinical Immunology | volume = 122 | issue = 6 | pages = 1178–841178–1184 | date = December 2008 | pmid = 18804272 | doi = 10.1016/j.jaci.2008.07.036 | doi-access = free }}</ref> The best characterised variant is an A-to-G [[Transition (genetics)|transition]] at nucleotide 70 that is in a loop region two bases 5' of a [[Conserved sequence|conserved]] [[pseudoknot]]. However, many other mutations within RNase MRP also cause CHH.

===Alzheimer's disease===

The antisense RNA, [[BACE1-AS]] is transcribed from the opposite strand to [[BACE1]] and is upregulated in patients with [[Alzheimer's disease]].<ref name="pmid18587408">{{cite journal | vauthors = Faghihi MA, Modarresi F, Khalil AM, Wood DE, Sahagan BG, Morgan TE, Finch CE, St Laurent G, Kenny PJ, Wahlestedt C | display-authors = 6 | title = Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase | journal = Nature Medicine | volume = 14 | issue = 7 | pages = 723–30723–730 | date = July 2008 | pmid = 18587408 | pmc = 2826895 | doi = 10.1038/nm1784 }}</ref> BACE1-AS regulates the expression of BACE1 by increasing BACE1 mRNA stability and generating additional BACE1 through a post-transcriptional feed-forward mechanism. By the same mechanism it also raises concentrations of [[beta amyloid]], the main constituent of senile plaques. BACE1-AS concentrations are elevated in subjects with Alzheimer's disease and in amyloid precursor protein transgenic mice.

===miR-96 and hearing loss===

Variation within the seed region of mature [[Mir-96 microRNA|miR-96]] has been associated with [[autosomal dominant]], progressive hearing loss in humans and mice. The [[homozygous]] mutant mice were profoundly deaf, showing no [[cochlea]]r responses. [[Heterozygous]] mice and humans progressively lose the ability to hear.<ref name="pmid19363479">{{cite journal | vauthors = Mencía A, Modamio-Høybjør S, Redshaw N, Morín M, Mayo-Merino F, Olavarrieta L, Aguirre LA, del Castillo I, Steel KP, Dalmay T, Moreno F, Moreno-Pelayo MA | display-authors = 6 | title = Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss | journal = Nature Genetics | volume = 41 | issue = 5 | pages = 609–13609–613 | date = May 2009 | pmid = 19363479 | doi = 10.1038/ng.355 | s2cid = 11113852 }}</ref><ref name="pmid19363478">{{cite journal | vauthors = Lewis MA, Quint E, Glazier AM, Fuchs H, De Angelis MH, Langford C, van Dongen S, Abreu-Goodger C, Piipari M, Redshaw N, Dalmay T, Moreno-Pelayo MA, Enright AJ, Steel KP | display-authors = 6 | title = An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice | journal = Nature Genetics | volume = 41 | issue = 5 | pages = 614–8614–618 | date = May 2009 | pmid = 19363478 | pmc = 2705913 | doi = 10.1038/ng.369 }}</ref><ref name="pmid19245798">{{cite journal | vauthors = Soukup GA | title = Little but loud: small RNAs have a resounding affect on ear development | journal = Brain Research | volume = 1277 | pages = 104–14104–114 | date = June 2009 | pmid = 19245798 | pmc = 2700218 | doi = 10.1016/j.brainres.2009.02.027 }}</ref>

===Mitochondrial transfer RNAs===

A number of mutations within mitochondrial tRNAs have been linked to diseases such as [[MELAS syndrome]], [[MERRF syndrome]], and [[chronic progressive external ophthalmoplegia]].<ref>{{cite journal |last1 vauthors = Taylor |first1=RW, |last2=Turnbull |first2=DM | title = Mitochondrial DNA mutations in human disease. | journal = Nature Reviews. Genetics |date=May 2005 |volume = 6 | issue = 5 | pages = 389–402 |doi date =10.1038/nrg1606 May 2005 | pmid = 15861210 | pmc = 1762815 | doi = 10.1038/nrg1606 }}</ref><ref>{{cite journal |last1 vauthors = Yarham |first1=JW, |last2=Elson |first2=JL, |last3=Blakely |first3=EL, |last4=McFarland |first4=R, |last5=Taylor |first5=RW | title = Mitochondrial tRNA mutations and disease. | journal = Wiley Interdisciplinary Reviews:. RNA |date=September 2010volume |volume= 1 | issue = 2 | pages =304–24 304–324 | date = September 2010 | pmid = 21935892 | doi = 10.1002/wrna.27 |pmid=21935892| s2cid = 43123827 }}</ref><ref>{{cite journal |last1 vauthors = Zifa |first1=E, |last2=Giannouli |first2=S, |last3=Theotokis |first3=P, |last4=Stamatis |first4=C, |last5=Mamuris |first5=Z, |last6=Stathopoulos |first6=C | title = Mitochondrial tRNA mutations: clinical and functional perturbations. | journal = RNA Biology |date=January 2007volume |volume= 4 | issue = 1 | pages = 38–66 | date = January 2007 | pmid = 17617745 | doi = 10.4161/rna.4.1.4548 |pmid=17617745| s2cid = 11965790 | doi-access = free }}</ref><ref>{{cite journal |last1 vauthors = Abbott |first1=JA, |last2=Francklyn |first2=CS, |last3=Robey-Bond |first3=SM | title = Transfer RNA and human disease. | journal = Frontiers in Genetics |date=2014 |volume = 5 | pages = 158 | date = 2014 | pmid = 24917879 | pmc = 4042891 | doi = 10.3389/fgene.2014.00158 |pmid=24917879|pmc=4042891 |doi-access = free }}</ref>

==Distinction between functional RNA (fRNA) and ncRNA==

Scientists have started to distinguish ''functional RNA'' (''fRNA'') from ncRNA, to describe regions functional at the RNA level that may or may not be stand-alone RNA transcripts.<ref>{{cite journal | vauthors = Carter RJ, Dubchak I, Holbrook SR | title = A computational approach to identify genes for functional RNAs in genomic sequences | journal = Nucleic Acids Research | volume = 29 | issue = 19 | pages = 3928–383928–3938 | date = October 2001 | pmid = 11574674 | pmc = 60242 | doi = 10.1093/nar/29.19.3928 }}</ref><ref>{{cite journal | vauthors = Pedersen JS, Bejerano G, Siepel A, Rosenbloom K, Lindblad-Toh K, Lander ES, Kent J, Miller W, Haussler D | display-authors = 6 | title = Identification and classification of conserved RNA secondary structures in the human genome | journal = PLOS Computational Biology | volume = 2 | issue = 4 | pages = e33 | date = April 2006 | pmid = 16628248 | pmc = 1440920 | doi = 10.1371/journal.pcbi.0020033 | doi-access = free | bibcode = 2006PLSCB...2...33P }}</ref><ref>{{cite journal | vauthors = Thomas JM, Horspool D, Brown G, Tcherepanov V, Upton C | title = GraphDNA: a Java program for graphical display of DNA composition analyses | journal = BMC Bioinformatics | volume = 8 | pagesarticle-number = 21 | date = January 2007 | pmid = 17244370 | pmc = 1783863 | doi = 10.1186/1471-2105-8-21 | doi-access = free }}</ref> This implies that fRNA (such as riboswitches, [[SECIS element]]s, and other cis-regulatory regions) is not ncRNA. Yet 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 name="Edd01" /> state that ''ncRNA'' and ''fRNA'' are nearly synonymous, however others have pointed out that a large proportion of annotated ncRNAs likely have no function.<ref name="waste"/><ref name="PalazzoLee2015"/> It also has been suggested to simply use the term ''RNA'', since the distinction from a protein coding RNA ([[messenger RNA]]) is already given by the qualifier ''mRNA''.<ref>{{cite journal | vauthors = Brosius J, Raabe CA | title = What is an RNA? A top layer for RNA classification | journal = RNA Biology | volume = 13 | issue = 2 | pages = 140–4140–144 | date = February 2015 | pmid = 26818079 | pmc = 4829331 | doi = 10.1080/15476286.2015.1128064 }}</ref> This eliminates the ambiguity when addressing a gene "encoding a non-coding" RNA. Besides, there may be a number of ncRNAs that are misannoted in published literature and datasets.<ref>{{Citecite journal |last1 vauthors = Ji|first1=Zhe|last2= Z, Song|first2=Ruisheng|last3= R, Regev|first3=Aviv|last4= A, Struhl K |first4=Kevin|date=2015-12-19| title = Many lncRNAs, 5'UTRs, and pseudogenes are translated and some are likely to express functional proteins | journal = eLife |language=en| volume = 4 |pages article-number = e08890 |doi date =10.7554/eLife.08890 December 2015 | pmid = 26687005 | pmc = 4739776 |issn doi =2050 10.7554/eLife.08890 | doi-084Xaccess = free }}</ref><ref>{{Citecite journal |last1 vauthors = Tosar|first1=Juan Pablo|last2=JP, Rovira|first2=Carlos|last3= C, Cayota A |first3=Alfonso|date=2018-01-22| title = Non-coding RNA fragments account for the majority of annotated piRNAs expressed in somatic non-gonadal tissues | language = En | journal = Communications Biology |language=En| volume = 1 | issue = 1 |pages article-number = 2 |doi date =10.1038/s42003 2018-01701-0001-722 | pmid = 30271890 | pmc = 6052916 |issn doi =2399 10.1038/s42003-3642017-0001-7 }}</ref><ref>{{Citecite journal |last1 vauthors = Housman|first1=Gali|last2= G, Ulitsky|first2=Igor|date=January 2016I | title = Methods for distinguishing between protein-coding and long noncoding RNAs and the elusive biological purpose of translation of long noncoding RNAs | journal = Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms | volume = 1859 | issue = 1 | pages = 31–40 | date = January 2016 | pmid = 26265145 | doi = 10.1016/j.bbagrm.2015.07.017|issn=0006-3002|pmid=26265145 }}</ref>

== See also ==

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{{reflist|32em|refs =

<ref name="pmid17571346">{{cite journal |author-link3=John Stamatoyannopoulos | vauthors = ((ENCODE Project Consortium)), Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, Margulies EH, Weng Z, Snyder M, Dermitzakis ET, Thurman RE, Kuehn MS, Taylor CM, Neph S, Koch CM, Asthana S, Malhotra A, Adzhubei I, Greenbaum JA, Andrews RM, Flicek P, Boyle PJ, Cao H, Carter NP, Clelland GK, Davis S, Day N, Dhami P, Dillon SC, Dorschner MO, Fiegler H, Giresi PG, Goldy J, Hawrylycz M, Haydock A, Humbert R, James KD, Johnson BE, Johnson EM, Frum TT, Rosenzweig ER, Karnani N, Lee K, Lefebvre GC, Navas PA, Neri F, Parker SC, Sabo PJ, Sandstrom R, Shafer A, Vetrie D, Weaver M, Wilcox S, Yu M, Collins FS, Dekker J, Lieb JD, Tullius TD, Crawford GE, Sunyaev S, Noble WS, Dunham I, Denoeud F, Reymond A, Kapranov P, Rozowsky J, Zheng D, Castelo R, Frankish A, Harrow J, Ghosh S, Sandelin A, Hofacker IL, Baertsch R, Keefe D, Dike S, Cheng J, Hirsch HA, Sekinger EA, Lagarde J, Abril JF, Shahab A, Flamm C, Fried C, Hackermüller J, Hertel J, Lindemeyer M, Missal K, Tanzer A, Washietl S, Korbel J, Emanuelsson O, Pedersen JS, Holroyd N, Taylor R, Swarbreck D, Matthews N, Dickson MC, Thomas DJ, Weirauch MT, Gilbert J, Drenkow J, Bell I, Zhao X, Srinivasan KG, Sung WK, Ooi HS, Chiu KP, Foissac S, Alioto T, Brent M, Pachter L, Tress ML, Valencia A, Choo SW, Choo CY, Ucla C, Manzano C, Wyss C, Cheung E, Clark TG, Brown JB, Ganesh M, Patel S, Tammana H, Chrast J, Henrichsen CN, Kai C, Kawai J, Nagalakshmi U, Wu J, Lian Z, Lian J, Newburger P, Zhang X, Bickel P, Mattick JS, Carninci P, Hayashizaki Y, Weissman S, Hubbard T, Myers RM, Rogers J, Stadler PF, Lowe TM, Wei CL, Ruan Y, Struhl K, Gerstein M, Antonarakis SE, Fu Y, Green ED, Karaöz U, Siepel A, Taylor J, Liefer LA, Wetterstrand KA, Good PJ, Feingold EA, Guyer MS, Cooper GM, Asimenos G, Dewey CN, Hou M, Nikolaev S, Montoya-Burgos JI, Löytynoja A, Whelan S, Pardi F, Massingham T, Huang H, Zhang NR, Holmes I, Mullikin JC, Ureta-Vidal A, Paten B, Seringhaus M, Church D, Rosenbloom K, Kent WJ, Stone EA, Batzoglou S, Goldman N, Hardison RC, Haussler D, Miller W, Sidow A, Trinklein ND, Zhang ZD, Barrera L, Stuart R, King DC, Ameur A, Enroth S, Bieda MC, Kim J, Bhinge AA, Jiang N, Liu J, Yao F, Vega VB, Lee CW, Ng P, Shahab A, Yang A, Moqtaderi Z, Zhu Z, Xu X, Squazzo S, Oberley MJ, Inman D, Singer MA, Richmond TA, Munn KJ, Rada-Iglesias A, Wallerman O, Komorowski J, Fowler JC, Couttet P, Bruce AW, Dovey OM, Ellis PD, Langford CF, Nix DA, Euskirchen G, Hartman S, Urban AE, Kraus P, Van Calcar S, Heintzman N, Kim TH, Wang K, Qu C, Hon G, Luna R, Glass CK, Rosenfeld MG, Aldred SF, Cooper SJ, Halees A, Lin JM, Shulha HP, Zhang X, Xu M, Haidar JN, Yu Y, Ruan Y, Iyer VR, Green RD, Wadelius C, Farnham PJ, Ren B, Harte RA, Hinrichs AS, Trumbower H, Clawson H, Hillman-Jackson J, Zweig AS, Smith K, Thakkapallayil A, Barber G, Kuhn RM, Karolchik D, Armengol L, Bird CP, de Bakker PI, Kern AD, Lopez-Bigas N, Martin JD, Stranger BE, Woodroffe A, Davydov E, Dimas A, Eyras E, Hallgrímsdóttir IB, Huppert J, Zody MC, Abecasis GR, Estivill X, Bouffard GG, Guan X, Hansen NF, Idol JR, Maduro VV, Maskeri B, McDowell JC, Park M, Thomas PJ, Young AC, Blakesley RW, Muzny DM, Sodergren E, Wheeler DA, Worley KC, Jiang H, Weinstock GM, Gibbs RA, Graves T, Fulton R, Mardis ER, Wilson RK, Clamp M, Cuff J, Gnerre S, Jaffe DB, Chang JL, Lindblad-Toh K, Lander ES, Koriabine M, Nefedov M, Osoegawa K, Yoshinaga Y, Zhu B, de Jong PJ | display-authors = 6 | title = Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project | journal = Nature | volume = 447 | issue = 7146 | pages = 799–816 | date = June 2007 | pmid = 17571346 | pmc = 2212820 | doi = 10.1038/nature05874 | collaboration = ENCODE Project Consortium | author-link3 = John Stamatoyannopoulos | bibcode = 2007Natur.447..799B }}</ref>

}}

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== External links ==

{{Commons category|Non-coding RNA}}

* [{{cite web | url = http://jsm-research.imb.uq.edu.au/rnadb/ | title = RNAdb | archive-url = https://web.archive.org/web/20070829173837/http://jsm-research.imb.uq.edu.au/rnadb/ Comprehensive| archive-date = 2007-08-29 | quote = This database ofis a comprehensive mammalian ncRNAs]noncoding RNA database (RNAdb) }}

([[Wayback Machine]] copy)

* [http://rfam.org/ The Rfam Database] — a curated list of hundreds of families of related ncRNAs

* [http://www.noncode.org/ NONCODE.org] — a free database of all kinds of noncoding RNAs (except tRNAs and rRNAs)

* [http://www.imtech.res.in/raghava/rnacon/ RNAcon] Prediction and classification of ncRNA [http://www.biomedcentral.com/1471-2164/15/127 BMC Genomics 2014, 15:127]

* [http://www.nature.com/encode/#/threads/non-coding-rna-characterization ENCODE threads explorer] Non-coding RNA characterization. [[Nature (journal)]]

* [https://nrdr.ncrnadatabases.org/ The Non-coding RNA Databases Resource (NRDR)] — a curated source of data related to over non-coding RNA databases available over the internet

*[https://lisanwanglab.org/DASHRv2 DASHR] - a database of small non-coding RNAs [https://doi.org/10.1093/bioinformatics/bty709 Bioinformatics 2018]