Editing Non-coding RNA (section)

==Roles in disease==

{{see also|Long noncoding RNA#Long non-coding RNAs in disease}}

As with [[protein]]s, mutations or imbalances in the ncRNA repertoire within the body can cause a variety of diseases.

===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 = 135–141 | 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 = 447–454 | 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 = 981–988 | 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 = 1817–1821 | date = December 2005 | pmid = 16308420 | doi = 10.1126/science.1121158 | s2cid = 1849875 | bibcode = 2005Sci...310.1817F }}</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 = 769–773 | date = February 2005 | pmid = 15685193 | doi = 10.1038/nature03315 | s2cid = 4430576 | bibcode = 2005Natur.433..769L }}</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.

[[Germline]] 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 = 1793–1801 | 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 = 15524–15529 | date = November 2002 | pmid = 12434020 | pmc = 137750 | doi = 10.1073/pnas.242606799 | doi-access = free | bibcode = 2002PNAS...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 = 2600–2608 | 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 = 1178–1182 | 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>{{cite journal | vauthors = Jia B, Wang Z, Sun X, Chen J, Zhao J, Qiu X | title = Long noncoding RNA LINC00707 sponges miR-370-3p to promote osteogenesis of human bone marrow-derived mesenchymal stem cells through upregulating WNT2B | journal = Stem Cell Research & Therapy | volume = 10 | issue = 1 | pages = 67 | date = February 2019 | pmid = 30795799 | pmc = 6387535 | doi = 10.1186/s13287-019-1161-9 | doi-access = free }}</ref> gastric cancer<ref>{{cite journal | vauthors = Xie M, Ma T, Xue J, Ma H, Sun M, Zhang Z, Liu M, Liu Y, Ju S, Wang Z, De W | display-authors = 6 | title = The long intergenic non-protein coding RNA 707 promotes proliferation and metastasis of gastric cancer by interacting with mRNA stabilizing protein HuR | journal = Cancer Letters | volume = 443 | pages = 67–79 | date = February 2019 | pmid = 30502359 | doi = 10.1016/j.canlet.2018.11.032 | s2cid = 54611497 }}</ref> or breast cancer,<ref>{{cite journal | vauthors = Li T, Li Y, Sun H | title = MicroRNA-876 is sponged by long noncoding RNA LINC00707 and directly targets metadherin to inhibit breast cancer malignancy | journal = Cancer Management and Research | volume = 11 | pages = 5255–5269 | date = 2019-06-06 | pmid = 31239777 | pmc = 6559252 | doi = 10.2147/cmar.s210845 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Yuan RX, Bao D, Zhang Y | title = Linc00707 promotes cell proliferation, invasion, and migration via the miR-30c/CTHRC1 regulatory loop in breast cancer | 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 | s2cid = 218759508 }}</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 = 719–721 | 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 | veditors = Akbarian S | doi-access = free | bibcode = 2008PLoSO...3.1709D }}</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 = 424–431 | 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 = 172–179 | 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 = 131–137 | 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 = 919–923 | date = October 2008 | pmid = 18923514 | doi = 10.1038/nature07458 | s2cid = 4377899 | bibcode = 2008Natur.455..919C }}</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 = 1235–1246 | 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 = 589–593 | 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 = 219–226 | 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 = 1178–1184 | 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 = 723–730 | 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 = 609–613 | 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 = 614–618 | 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 = 104–114 | 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 | vauthors = Taylor RW, Turnbull DM | title = Mitochondrial DNA mutations in human disease | journal = Nature Reviews. Genetics | volume = 6 | issue = 5 | pages = 389–402 | date = May 2005 | pmid = 15861210 | pmc = 1762815 | doi = 10.1038/nrg1606 }}</ref><ref>{{cite journal | vauthors = Yarham JW, Elson JL, Blakely EL, McFarland R, Taylor RW | title = Mitochondrial tRNA mutations and disease | journal = Wiley Interdisciplinary Reviews. RNA | volume = 1 | issue = 2 | pages = 304–324 | date = September 2010 | pmid = 21935892 | doi = 10.1002/wrna.27 | s2cid = 43123827 }}</ref><ref>{{cite journal | vauthors = Zifa E, Giannouli S, Theotokis P, Stamatis C, Mamuris Z, Stathopoulos C | title = Mitochondrial tRNA mutations: clinical and functional perturbations | journal = RNA Biology | volume = 4 | issue = 1 | pages = 38–66 | date = January 2007 | pmid = 17617745 | doi = 10.4161/rna.4.1.4548 | s2cid = 11965790 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Abbott JA, Francklyn CS, Robey-Bond SM | title = Transfer RNA and human disease | journal = Frontiers in Genetics | volume = 5 | pages = 158 | date = 2014 | pmid = 24917879 | pmc = 4042891 | doi = 10.3389/fgene.2014.00158 | doi-access = free }}</ref>