Lnc-C9orf53-2:1

CDKN2B-AS1, Antisense long noncoding RNA of the INK4b/ARF/INK4a locus is important for expression of the protein-coding genes in cis

Annotated Information

Approved Symbol

CDKN2B-AS1

Approved Name

CDKN2B-AS1 ANRIL: Antisense noncoding RNA in the INK4 locus; CDKN2B-AS1: CDKN2B antisense RNA 1; P15AS: P15 antisense RNA

Characteristics

CDKN2B-AS1 is present in multiple splicing isoforms such as the CDK2BAS RefSeq sequence NR_003529.3 of ~3.9kb. ^[1] CDKN2B-AS1 is detected as an unspliced transcript of 34.8 kb specified as p15AS. ^[2] CDKN2B-AS1 is Antisense to the tumor suppressor gene p15/CDKN2A. ^[2] Traverses a noncoding region centromeric to CDKN2A, a region containing the INK4b/ARF/INK4a locus and implicated in a range of complex diseases including cancer (such as melanoma-neural system tumor syndrome), type 2 diabetes, periodontitis and coronary heart disease. ^[3] Transcript of CDKN2B-AS1 is found to be quite unstable with a half-life >4 hr in human Hela cell. ^[4]

Function

CDKN2B-AS1 RNA was found to interact and regulate chromobox 7 (CBX7), a component of the Polycomb Repressor Complex 1 (PRC1), which methylates histone H3 lysine 27 to promote epigenetic silencing, and is also up-regulated in prostate cancer. Interaction occurs with a conserved chromodomain of CBX7 and is essential for the ability of PRC1 to repress the INK4b/ARF/INK4a locus and control cell senescence. ^[5]

Regulation

CDKN2B-AS1 is controlled by methylation of histone H3 at lysine 27 (H3K27me). ^[5]

Disease

Aortic aneurysm ^[1]
Atherosclerosis susceptibility ^[6]
Intracranial aneurysm ^[7]
Periodontitis ^[6]

Expression

CDKN2B-AS1 is expressed in tissues and cell types affected by atherosclerosis. Increased levels of CDKN2B-AS1 are found in patients carrying the atherosclerosis risk haplotype expression, including in peripheral blood mononuclear cells, whole blood and atherosclerotic plaque tissue, and the levels were directly correlated with the severity of atherosclerosis. ^[8] it is up-regulated in prostate cancer. ^[5]

Labs working on this lncRNA

Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Liebigstr. 27, 04103 Leipzig, Germany
Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, NY 10029, USA
Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo, Japan
Cell Proliferation Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Campus, London, UK
Center for Epigenetics and Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, Maryland 21205, USA
Department of Medicine, Karolinska Institute, Stockholm, Sweden

References

↑ ^1.0 ^1.1 Folkersen L, Kyriakou T, Goel A, Peden J, Malarstig A, Paulsson-Berne G et al. Relationship between CAD Risk Genotype in the Chromosome 9p21 Locus and Gene Expression. Identification of Eight New ANRIL Splice Variants[J]. Plos One. 2009, 4(11).
↑ ^2.0 ^2.1 Yu WQ, Gius D, Onyango P, Muldoon-Jacobs K, Karp J, Feinberg AP et al. Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA[J]. Nature. 2008, 451(7175):202-U210.
↑ Popov N & Gil J. Epigenetic regulation of the INK4b-ARF-INK4a locus In sickness and in health[J]. Epigenetics-Us. 2010, 5(8):685-690.
↑ Tani H, Mizutani R, Salam KA, Tano K, Ijiri K, Wakamatsu A et al. Genome-wide determination of RNA stability reveals hundreds of short-lived non-coding transcripts in mammals[J]. Genome research. 2012,gr. 130559.130111.
↑ ^5.0 ^5.1 ^5.2 Popov N & Gil J. Epigenetic regulation of the INK4b-ARF-INK4a locus In sickness and in health[J]. Epigenetics-Us. 2010, 5(8):685-690.
↑ ^6.0 ^6.1 Bochenek G, Häsler R, El Mokhtari N-E, König IR, Loos BG, Jepsen S et al. The large non-coding RNA ANRIL, which is associated with atherosclerosis, periodontitis and several forms of cancer, regulates ADIPOR1, VAMP3 and C11ORF10[J]. Human molecular genetics. 2013, 22(22):4516-4527.
↑ Pasmant E, Sabbagh A, Vidaud M & Bièche I. ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS[J]. The FASEB Journal. 2011, 25(2):444-448.
↑ Holdt LM, Beutner F, Scholz M, Gielen S, Gäbel Gb, Bergert H et al. ANRIL expression is associated with atherosclerosis risk at chromosome 9p21[J]. Arteriosclerosis, thrombosis, and vascular biology. 2010, 30(3):620-627.

Sequence

>gi|100048912|ref|NR_003529.3|Homo sapiens CDKN2B antisense RNA 1 (CDKN2B-AS1), transcript variant 1, long non-coding RNA

000001  AGCTACATCC GTCACCTGAC ACGGCCCTAC CAGGAACAGC CGCGCTCCCG CGGATTCTGG TGCTGCTCGC GTCCCCGCTC  000080
000081  CCCTATTCCC CTTATTTTAT TCCTGGCTCC CCTCGTCGAA AGTCTTCCAT TCTTCAAACT AGATTATTTA AAAATGAAAA  000160
000161  AGGAAGAAAG GAAAGCGAGG TCATCTCATT GCTCTATCCG CCAATCAGGA GGCTGAATGT CAGTTTTGAA CTAAAAGCCG  000240
000241  CTCCGCTCCT CTTCTAGATT TGGAAAACAA GCGAAATTAA ACTAAACCGC TGCACGCCTC TGACGCGACA TCTGGACACG  000320
000321  GCGCGGCGCT GGCGCTGCCG GAGCTGTCGA CCCGGCCTGG CGCCGGACTA GGACTATTTG CCACGACATT TCAAAGGATT  000400
000401  CCAAGAGAGA ATATTGGTGT CCATGCTGTG ATGATTCCTC AGCTCCTCTC ATCTGATCTC CGTCCTGGCC CCCATGACTT  000480
000481  TCTTTGTGGT AGTTAGGGTG TGGTATGTGC CACTGAGGCC CACACCTATT GCTGCAATTT ATAGCACTGA TCTGTCATCA  000560
000561  ATACCACTTG CTGTCTTGGA TGTGAAGATG ATTTTTCCTG CAGGGATTCC CTCTACAAAA TTAAAAACAC TGGGCATGTG  000640
000641  GAAATAATAT TCATGCTTTA AATTGTCTTT TCTCTTCACT ACACCAGGGG TCCCCAACCC CTAGGCCACA GACTGTGGCC  000720
000721  CTAGTGTAGT GAATAGAAAA GACAATTTAA AGCGTGAATA TTATTTCCTC ATGCCCAGTG TTTTTAATTT TGTACTGGTC  000800
000801  TGTGGCTTGT TAGAAACCAG GCTGCACAGC AGAAGGTGGG CAGCAGATAT TGAGAAACCA CAGAAAGAGA GAAGTTAAAT  000880
000881  AATTTTCCTG TCAAAGACCA CATCAATGAT GAAGCCAGAA TTTGAGCTCA TGTACTTAAC CACTGGACTA CCTGCCTGCC  000960
000961  CTGTCGAGGA ACAGCTAAGT GTCCCTTTTG ATGAGAAGAA TAAGCCTCAT TCTGATTCAA CAGCAGAGAT CAAAGAAAAG  001040
001041  ACTTCTGTTT TCTGGCCACC AGATATATGT TATCTGTGCT TAAAGAATTG AAAAACACAC ATCAAAGGAG AATTTTCTTG  001120
001121  GAAAGAGAGG GTTCAAGCAT CACTGTTAGG TGTGCTGGAA TCCTTTCCCG AGTCAGTACT GCTTTCTAGA AGAAAACCGG  001200
001201  GGAGATCTAT TTGGAATGTA TCTAACTCCA AAGAAACCAT CAGAGGTAAC AGTAGAGACG GGGTTTCACC ATGTTGGCCA  001280
001281  GACTGGTCTT GAACTCTCGA CCTCGTGATT CGCCCGCCTC GGCCTCCCAA AGTGCTGGGA TTACAGGTGT GAGACACCAC  001360
001361  ACCCGGCGGA TAGAGAGAAT TTTGACAGTC TCTCCAATGA ACGCCTTCAC TGATATCCAA AGCATGAAGG ACACACCAGG  001440
001441  GAAAAACATA GACCTAACAC AGGACAAATG GAATTATTAG AAACATTTTC TAGCAGAAGA ACACTATTCT GTTGCCATTT  001520
001521  GAATCTTTGC TTCTTTCTAG GTTTGACAAT GAGCCTATCA TATAAGCCCA AATGTAAACA GAAAGAGGTT GAATCAGTCA  001600
001601  CGATAAGCCC AATTATGCTG TGGTAACAAA CAACCTCAAA ATCTCATTGG CTTAAAATAT ACAGAATTAT TCTTACTCAT  001680
001681  GGCACATATC CATCTATCAT CTGCAGGGGA TCTGCTCACT GAAGTCACTT AGGAACTTGG ACTGATGGAA CGGCCACTTT  001760
001761  TTGGTCACTA TATGTATTAA TCTGTTTTAA TCCTGCTGAT AAAGACCCAA AATTGGGAAC AAAAAGAAGT TTAACTAGAC  001840
001841  TTACAGTTCC GCATGGCTGA GGAGGCCTCA GAATCATGGT GGGAGGCGAA AGGCACTTCT TACATGGTGG CAGCAAGAGA  001920
001921  AAAATGAGGA AGAAGCAAAA GCGGAAACCT CTGATAAACC CATCAGATCT TATGAGACTT ATTCCACTAT CAAGAGAATA  002000
002001  GCATGGGAAA GACTGGCTCC CATAATTTAC CTCCCTCTGG GTCCCTCCCT CAACATGTGG GAATTCTGGG AGAAACAATT  002080
002081  CAAGATATGA CACATTCATA ATTTAAACAG AAGCCTACGA AGAACTCATA AATTAAAAGA AGATAATCTT TTCACAAGGT  002160
002161  GATGGAGGCT TTTTATTTTG CCACAAAACC ACTGGTGACG TTGCCTGTGG CCACCTTGGA GAAGACACTG GAGGCCTGGG  002240
002241  ACATGGAGAC TGCTTTTCTG CAGAAACCAC ATCCCTTGGA GTAATGAGCT ACACCTACCT CAATTATTCA GTGCAGTACA  002320
002321  ACACTCCAGA CAGGGTCTCA CTCTGTCACC CAGGCTGGAG TGTATTGGCA TGATTACAGC TCACTGCAAC CTTGAACTCC  002400
002401  CAGGCTCAAA CCTGAGCAGC TGGGACTACA GATGCACCAC CATGCATGGT ACCAGAGATA TAATAATGAG AAACAGACAT  002480
002481  GCTCCCTCCC CTCATTGAGG TTACAGCTTA GTGTGGAGAC ACACAGATGC CTAACGCACT ATGGTATGGA AGGTGCTATG  002560
002561  GACACAGTGC TCAAATCCAT GATCTACATA GGTGGAGAAC TTCAGTAGAG GAAGTGGCAG GAATTTGGGA ATGAGGAGCA  002640
002641  CAGTGATTAA ACTGGGGCCA TTCATATGAG AGTTTAAGAA CTCAGACCAG TGACTTAGAT TGGCTTCTCT CACATGGCAA  002720
002721  GAAACATTGC TGCTAGCACT TCCCGAGTTC TACGTTCTAC AACATCCACC ACTGGATCTT AACATAGACG TAAGATCAAA  002800
002801  TGCAATAGCA TGTCAAACAA TGTGTAACTC CAGTTATACA AACATTACTG TATCTCATTG GGGATACGAA GCTCTACACA  002880
002881  CTTGAAGATG GTGAAGGAAT ATAAAAATCT ATGTCTCACA GTCCAGACTT GGAGTACAAG TAATAAGAAG AATAAAACTT  002960
002961  AATCCCTTAA GTAGATTCAC CATAAGTTAG CTCAGAGCAA TTCCAGTGCA AGTATGGTCT GTGATCCAGT AGTATCTTAC  003040
003041  AGACAGCAAG TTGAACATTG TGGGATGCAT GAGCTATTGA GGCCTTTGCA GCTTTCTGCT ACATGGAGGC TAGGGCCAGA  003120
003121  GTCAAGATTT ATGCTTTGCA GCACACTGGT CAGCTGTTTT TGCAAATCAG ATTAAATGAT TTTTAAATGA GGCTGAGAGC  003200
003201  ATGGGAGATA CTAATGTGTG TTTCCTTGTG AGCTACTGCA TAAGTTAGGA AATTGAAATA CAGAAAGATG AAAAGTGATT  003280
003281  TGCCCAAGCA TATAGATCAA AGCTGTGGCA GAACCAGGAC TGGAACCTAT ATCTCTCTAC TAATGGTTTT TTTAAAAAAA  003360
003361  TAACCTTGTT TCAAAAATAT TAAAAAGTCA CAAGAAAGGT AAACATGTGG ATAAACAAAA TGAAGAAAAT AAAAATTATC  003440
003441  CAGTAATAAC ATATTGGCAT ATGTCTTTCT GGTATATTTT CCTGTGTTGT CATCATTATC ATCTCCATCA TCATTATATC  003520
003521  CATCATTATC ATCATCATCA TCATCATCAT CATCATTATC ATCACCA

[ref1-1] 1.0 ^1.1 Folkersen L, Kyriakou T, Goel A, Peden J, Malarstig A, Paulsson-Berne G et al. Relationship between CAD Risk Genotype in the Chromosome 9p21 Locus and Gene Expression. Identification of Eight New ANRIL Splice Variants[J]. Plos One. 2009, 4(11).

[ref2-2] 2.0 ^2.1 Yu WQ, Gius D, Onyango P, Muldoon-Jacobs K, Karp J, Feinberg AP et al. Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA[J]. Nature. 2008, 451(7175):202-U210.

[ref3-3] Popov N & Gil J. Epigenetic regulation of the INK4b-ARF-INK4a locus In sickness and in health[J]. Epigenetics-Us. 2010, 5(8):685-690.

[ref4-4] Tani H, Mizutani R, Salam KA, Tano K, Ijiri K, Wakamatsu A et al. Genome-wide determination of RNA stability reveals hundreds of short-lived non-coding transcripts in mammals[J]. Genome research. 2012,gr. 130559.130111.

[ref5-5] 5.0 ^5.1 ^5.2 Popov N & Gil J. Epigenetic regulation of the INK4b-ARF-INK4a locus In sickness and in health[J]. Epigenetics-Us. 2010, 5(8):685-690.

[ref8-6] 6.0 ^6.1 Bochenek G, Häsler R, El Mokhtari N-E, König IR, Loos BG, Jepsen S et al. The large non-coding RNA ANRIL, which is associated with atherosclerosis, periodontitis and several forms of cancer, regulates ADIPOR1, VAMP3 and C11ORF10[J]. Human molecular genetics. 2013, 22(22):4516-4527.

[ref7-7] Pasmant E, Sabbagh A, Vidaud M & Bièche I. ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS[J]. The FASEB Journal. 2011, 25(2):444-448.

[ref6-8] Holdt LM, Beutner F, Scholz M, Gielen S, Gäbel Gb, Bergert H et al. ANRIL expression is associated with atherosclerosis risk at chromosome 9p21[J]. Arteriosclerosis, thrombosis, and vascular biology. 2010, 30(3):620-627.

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