Editing Non-coding RNA (section)

==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 | pmc = 7327968 | doi = 10.2174/1389202920666191129112705 }}</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 fossil]]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 }}</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 }}</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 = 880–889 | 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 = 905–920 | date = August 2000 | pmid = 10937989 | doi = 10.1126/science.289.5481.905 | citeseerx = 10.1.1.58.2271 | bibcode = 2000Sci...289..905B }}</ref> The small patch of green in the center of the subunit is the active site.]]
===In translation===

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===

[[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 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 = 230–232 | date = January 2006 | pmid = 16357227 | doi = 10.1126/science.1118265 | s2cid = 44527461 | doi-access = free | bibcode = 2006Sci...311..230K }}</ref>

In nematodes, the [[SmY]] ncRNA appears to be involved in mRNA [[trans-splicing]].<ref>{{Cite journal |last1=Jones |first1=Thomas A. |last2=Otto |first2=Wolfgang |last3=Marz |first3=Manja |last4=Eddy |first4=Sean R. |last5=Stadler |first5=Peter F. |date=2009 |title=A survey of nematode SmY RNAs |url=https://pubmed.ncbi.nlm.nih.gov/19106623/ |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 = 529–539 | 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 = 2058–2069 | 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 = 103–110 | 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 = 400–402 | date = January 1981 | pmid = 6164096 | doi = 10.1126/science.6164096 | bibcode = 1981Sci...211..400L }}</ref>

===In gene regulation===

The [[Gene expression|expression]] of many thousands of [[gene]]s are regulated by ncRNAs.  This regulation can occur in [[Trans-acting|trans]] or in [[Cis-acting|cis]]. There is increasing evidence that a special type of ncRNAs called [[enhancer RNAs]], transcribed from the enhancer region of a gene, act to promote gene expression.{{citation needed|date=June 2017}}

====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 complementarity 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 = 1621–1635 | 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}}

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 sequence]]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 = 822–829 | 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 = 130–134 | date = November 2008 | pmid = 18820678 | doi = 10.1038/nature07348 | s2cid = 4416402 | bibcode = 2008Natur.456..130H }}</ref>

====Cis-acting====

{{Main|Five prime untranslated region|Three prime untranslated region}}

A number of ncRNAs are embedded in the 5' [[Untranslated Region|UTRs]] (Untranslated Regions) of [[mRNA|protein coding genes]] and influence their expression in various ways. For example, a [[riboswitch]] can directly bind a [[Small molecule|small target molecule]]; the binding of the target affects the gene's activity.{{citation needed|date=June 2017}}

[[Attenuator (genetics)|RNA leader]] sequences are found upstream of the first gene of amino acid biosynthetic operons. These [[cis-regulatory element|RNA elements]] form one of two possible structures in regions encoding very short peptide sequences that are rich in the end product amino acid of the operon. A terminator structure forms when there is an excess of the regulatory amino acid and ribosome movement over the leader transcript is not impeded. When there is a deficiency of the charged tRNA of the regulatory amino acid the ribosome translating the leader peptide stalls and the antiterminator structure forms. This allows RNA polymerase to transcribe the operon. Known RNA leaders are [[Histidine operon leader]], [[Leucine operon leader]], [[Threonine operon leader]] and the [[Tryptophan operon leader]].{{citation needed|date=June 2017}}

[[Iron response element]]s (IRE) are bound by [[Iron-responsive element binding protein|iron response proteins]] (IRP).  The IRE is found in UTRs of various [[mRNA]]s whose products are involved in [[iron metabolism]].  When iron concentration is low, IRPs bind the ferritin mRNA IRE leading to translation repression.{{citation needed|date=June 2017}}

[[Internal ribosome entry site]]s (IRES) are [[RNA structure]]s that allow for [[translation (genetics)|translation]] initiation in the middle of a mRNA sequence as part of the process of [[protein synthesis]].{{citation needed|date=June 2017}}

===In genome defense===

[[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 [[germline]] 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.

===Chromosome structure===

[[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 = 1620–1623 | date = November 2002 | pmid = 12446910 | doi = 10.1126/science.1076686 | s2cid = 27167367 | bibcode = 2002Sci...298.1620P }}</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 = 20454–20459 | date = December 2007 | pmid = 18042713 | pmc = 2154452 | doi = 10.1073/pnas.0708102104 | doi-access = free | bibcode = 2007PNAS..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 | veditors = McEntyre J | doi-access = free | bibcode = 2008PLSCB...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 | veditors = Goldberg DE | doi-access = free }}</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 = 519–528 | 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 | 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 = 4119–4129 | date = December 1996 | pmid = 9012531 | doi = 10.1242/dev.122.12.4119 | 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 = 3445–3457 | 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 = 2827–2833 | 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 = 3144–3152 | 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 = 1098–1105 | date = September 2008 | pmid = 19160491 | doi = 10.1038/ncb1770 | s2cid = 5122088 }}</ref> [[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 = 11659–11672 | date = December 2012 | pmid = 23034808 | pmc = 3526287 | doi = 10.1093/nar/gks895 }}</ref> and [[Spot 42 RNA]].<ref name="pmid35239441">{{cite journal | 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 | pages = 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-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 = 1132–1147 | 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 = 151–160 | 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 = 516–520 | 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 | vauthors = Kaletsky R, Moore RS, Vrla GD, Parsons LR, Gitai Z, Murphy CT | title = C. elegans interprets bacterial non-coding RNAs to learn pathogenic avoidance | journal = Nature | volume = 586 | issue = 7829 | pages = 445–451 | date = October 2020 | pmid = 32908307 | pmc = 8547118 | doi = 10.1038/s41586-020-2699-5 | s2cid = 221626129 | bibcode = 2020Natur.586..445K }}</ref>