CDKN2BAS explained

CDKN2B-AS, also known as ANRIL (antisense non-coding RNA in the INK4 locus) is a long non-coding RNA consisting of 19 exons, spanning 126.3kb in the genome, and its spliced product is a 3834bp RNA. It is located within the p15/CDKN2B-p16/CDKN2A-p14/ARF gene cluster, in the antisense direction. Single nucleotide polymorphisms (SNPs) which alter the expression of CDKN2B-AS are associated with human healthy life expectancy, as well as with multiple diseases, including coronary artery disease, diabetes and many cancers.^[1] It binds to chromobox 7 (CBX7) within the polycomb repressive complex 1 and to SUZ12, a component of polycomb repression complex 2 and through these interactions is involved in transcriptional repression.^{[2] [3]}

See also

• Long noncoding RNA

Further reading

• Mußotter T, Kluwe L, Högel J, Nguyen R, Cooper DN, Mautner VF, Kehrer-Sawatzki H . Non-coding RNA ANRIL and the number of plexiform neurofibromas in patients with NF1 microdeletions . BMC Medical Genetics . 13 . 98 . October 2012 . 23101500 . 3500256 . 10.1186/1471-2350-13-98 . free .
• McPherson R, Pertsemlidis A, Kavaslar N, Stewart A, Roberts R, Cox DR, Hinds DA, Pennacchio LA, Tybjaerg-Hansen A, Folsom AR, Boerwinkle E, Hobbs HH, Cohen JC . 6 . A common allele on chromosome 9 associated with coronary heart disease . Science . 316 . 5830 . 1488–1491 . June 2007 . 17478681 . 2711874 . 10.1126/science.1142447 . 2007Sci...316.1488M .
• Folkersen L, Kyriakou T, Goel A, Peden J, Mälarstig A, Paulsson-Berne G, Hamsten A, Franco-Cereceda A, Gabrielsen A, Eriksson P . 6 . Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants . PLOS ONE . 4 . 11 . e7677 . November 2009 . 19888323 . 2765615 . 10.1371/journal.pone.0007677 . Reitsma . free . 2009PLoSO...4.7677F . Pieter H. .
• Uno S, Zembutsu H, Hirasawa A, Takahashi A, Kubo M, Akahane T, Aoki D, Kamatani N, Hirata K, Nakamura Y . 6 . A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese . Nature Genetics . 42 . 8 . 707–710 . August 2010 . 20601957 . 10.1038/ng.612 . 205356736 .
• Wrensch M, Jenkins RB, Chang JS, Yeh RF, Xiao Y, Decker PA, Ballman KV, Berger M, Buckner JC, Chang S, Giannini C, Halder C, Kollmeyer TM, Kosel ML, LaChance DH, McCoy L, O'Neill BP, Patoka J, Pico AR, Prados M, Quesenberry C, Rice T, Rynearson AL, Smirnov I, Tihan T, Wiemels J, Yang P, Wiencke JK . 6 . Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility . Nature Genetics . 41 . 8 . 905–908 . August 2009 . 19578366 . 2923561 . 10.1038/ng.408 .
• Bilguvar K, Yasuno K, Niemelä M, Ruigrok YM, von Und Zu Fraunberg M, van Duijn CM, van den Berg LH, Mane S, Mason CE, Choi M, Gaál E, Bayri Y, Kolb L, Arlier Z, Ravuri S, Ronkainen A, Tajima A, Laakso A, Hata A, Kasuya H, Koivisto T, Rinne J, Ohman J, Breteler MM, Wijmenga C, State MW, Rinkel GJ, Hernesniemi J, Jääskeläinen JE, Palotie A, Inoue I, Lifton RP, Günel M . 6 . Susceptibility loci for intracranial aneurysm in European and Japanese populations . Nature Genetics . 40 . 12 . 1472–1477 . December 2008 . 18997786 . 2682433 . 10.1038/ng.240 .
• Sato K, Nakagawa H, Tajima A, Yoshida K, Inoue I . ANRIL is implicated in the regulation of nucleus and potential transcriptional target of E2F1 . Oncology Reports . 24 . 3 . 701–707 . September 2010 . 20664976 . 10.3892/or_00000910 . free .
• Yasuno K, Bilguvar K, Bijlenga P, Low SK, Krischek B, Auburger G, Simon M, Krex D, Arlier Z, Nayak N, Ruigrok YM, Niemelä M, Tajima A, von und zu Fraunberg M, Dóczi T, Wirjatijasa F, Hata A, Blasco J, Oszvald A, Kasuya H, Zilani G, Schoch B, Singh P, Stüer C, Risselada R, Beck J, Sola T, Ricciardi F, Aromaa A, Illig T, Schreiber S, van Duijn CM, van den Berg LH, Perret C, Proust C, Roder C, Ozturk AK, Gaál E, Berg D, Geisen C, Friedrich CM, Summers P, Frangi AF, State MW, Wichmann HE, Breteler MM, Wijmenga C, Mane S, Peltonen L, Elio V, Sturkenboom MC, Lawford P, Byrne J, Macho J, Sandalcioglu EI, Meyer B, Raabe A, Steinmetz H, Rüfenacht D, Jääskeläinen JE, Hernesniemi J, Rinkel GJ, Zembutsu H, Inoue I, Palotie A, Cambien F, Nakamura Y, Lifton RP, Günel M . 6 . Genome-wide association study of intracranial aneurysm identifies three new risk loci . Nature Genetics . 42 . 5 . 420–425 . May 2010 . 20364137 . 2861730 . 10.1038/ng.563 .
• Broadbent HM, Peden JF, Lorkowski S, Goel A, Ongen H, Green F, Clarke R, Collins R, Franzosi MG, Tognoni G, Seedorf U, Rust S, Eriksson P, Hamsten A, Farrall M, Watkins H . 6 . Susceptibility to coronary artery disease and diabetes is encoded by distinct, tightly linked SNPs in the ANRIL locus on chromosome 9p . Human Molecular Genetics . 17 . 6 . 806–814 . March 2008 . 18048406 . 10.1093/hmg/ddm352 . free .
• Hashikata H, Liu W, Inoue K, Mineharu Y, Yamada S, Nanayakkara S, Matsuura N, Hitomi T, Takagi Y, Hashimoto N, Miyamoto S, Koizumi A . 6 . Confirmation of an association of single-nucleotide polymorphism rs1333040 on 9p21 with familial and sporadic intracranial aneurysms in Japanese patients . Stroke . 41 . 6 . 1138–1144 . June 2010 . 20395613 . 10.1161/STROKEAHA.109.576694 . free . 2433/142049 . free .
• Helgadottir A, Thorleifsson G, Manolescu A, Gretarsdottir S, Blondal T, Jonasdottir A, Jonasdottir A, Sigurdsson A, Baker A, Palsson A, Masson G, Gudbjartsson DF, Magnusson KP, Andersen K, Levey AI, Backman VM, Matthiasdottir S, Jonsdottir T, Palsson S, Einarsdottir H, Gunnarsdottir S, Gylfason A, Vaccarino V, Hooper WC, Reilly MP, Granger CB, Austin H, Rader DJ, Shah SH, Quyyumi AA, Gulcher JR, Thorgeirsson G, Thorsteinsdottir U, Kong A, Stefansson K . 6 . A common variant on chromosome 9p21 affects the risk of myocardial infarction . Science . 316 . 5830 . 1491–1493 . June 2007 . 17478679 . 10.1126/science.1142842 . 71851374 . 2007Sci...316.1491H .
• Yang XR, Liang X, Pfeiffer RM, Wheeler W, Maeder D, Burdette L, Yeager M, Chanock S, Tucker MA, Goldstein AM . 6 . Associations of 9p21 variants with cutaneous malignant melanoma, nevi, and pigmentation phenotypes in melanoma-prone families with and without CDKN2A mutations . Familial Cancer . 9 . 4 . 625–633 . December 2010 . 20574843 . 3233727 . 10.1007/s10689-010-9356-3 .
• Shete S, Hosking FJ, Robertson LB, Dobbins SE, Sanson M, Malmer B, Simon M, Marie Y, Boisselier B, Delattre JY, Hoang-Xuan K, El Hallani S, Idbaih A, Zelenika D, Andersson U, Henriksson R, Bergenheim AT, Feychting M, Lönn S, Ahlbom A, Schramm J, Linnebank M, Hemminki K, Kumar R, Hepworth SJ, Price A, Armstrong G, Liu Y, Gu X, Yu R, Lau C, Schoemaker M, Muir K, Swerdlow A, Lathrop M, Bondy M, Houlston RS . 6 . Genome-wide association study identifies five susceptibility loci for glioma . Nature Genetics . 41 . 8 . 899–904 . August 2009 . 19578367 . 4501476 . 10.1038/ng.407 .
• Bei JX, Li Y, Jia WH, Feng BJ, Zhou G, Chen LZ, Feng QS, Low HQ, Zhang H, He F, Tai ES, Kang T, Liu ET, Liu J, Zeng YX . 6 . A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci . Nature Genetics . 42 . 7 . 599–603 . July 2010 . 20512145 . 10.1038/ng.601 . 205356689 .
• Turnbull C, Ahmed S, Morrison J, Pernet D, Renwick A, Maranian M, Seal S, Ghoussaini M, Hines S, Healey CS, Hughes D, Warren-Perry M, Tapper W, Eccles D, Evans DG, Hooning M, Schutte M, van den Ouweland A, Houlston R, Ross G, Langford C, Pharoah PD, Stratton MR, Dunning AM, Rahman N, Easton DF . 6 . Genome-wide association study identifies five new breast cancer susceptibility loci . Nature Genetics . 42 . 6 . 504–507 . June 2010 . 20453838 . 3632836 . 10.1038/ng.586 .
• Schaefer AS, Richter GM, Groessner-Schreiber B, Noack B, Nothnagel M, El Mokhtari NE, Loos BG, Jepsen S, Schreiber S . 6 . Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis . PLOS Genetics . 5 . 2 . e1000378 . February 2009 . 19214202 . 2632758 . 10.1371/journal.pgen.1000378 . Marchini . Jonathan . free .
• Chen L, Qu H, Guo M, Zhang Y, Cui Y, Yang Q, Bai R, Shi D . 6 . ANRIL and atherosclerosis . Journal of Clinical Pharmacy and Therapeutics . 45 . 2 . 240–248 . April 2020 . 31703157 . 10.1111/jcpt.13060 . 207956113 . free .

Notes and References

1. Cunnington MS, Santibanez Koref M, Mayosi BM, Burn J, Keavney B . Chromosome 9p21 SNPs Associated with Multiple Disease Phenotypes Correlate with ANRIL Expression . PLOS Genetics . 6 . 4 . e1000899 . April 2010 . 20386740 . 2851566 . 10.1371/journal.pgen.1000899 . Gibson . Greg . free .
2. Yap KL, Li S, Muñoz-Cabello AM, Raguz S, Zeng L, Mujtaba S, Gil J, Walsh MJ, Zhou MM . 6 . Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a . Molecular Cell . 38 . 5 . 662–674 . June 2010 . 20541999 . 2886305 . 10.1016/j.molcel.2010.03.021 .
3. Kotake Y, Nakagawa T, Kitagawa K, Suzuki S, Liu N, Kitagawa M, Xiong Y . Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene . Oncogene . 30 . 16 . 1956–1962 . April 2011 . 21151178 . 3230933 . 10.1038/onc.2010.568 .