Lnc-C9orf53-2:1

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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

Name

Approved symbol: CDKN2B-AS1

Approved name: CDKN2B antisense RNA 1

HGNC ID: HGNC:34341

Previous symbols: CDKN2BAS

Previous names: CDKN2B antisense RNA (non-protein coding)

Alias symbols: ANRIL; RP11-145E5.4; NCRNA00089; p15AS; CDKN2B-AS; PCAT12

Alias names: antisense RNA in the INK4 locus; non-protein coding RNA 89; p15 antisense RNA; CDKN2B antisense RNA (non-protein coding) ; prostate cancer associated transcript 12

RefSeq ID: NR_003529

LncBook ID: HSALNT0147433

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]

ANRIL suppress the expression of INK4a, INK4b and ARF at the late-stage of DNA damage response, allowing the cell to return to normal at the completion of the DNA repair.[6]

Regulation

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

ANRIL, is transcriptionally up-regulated by the transcription factor E2F1 in ATM-dependent manner following DNA damage.[6]

Disease

  • Aortic aneurysm [1]
  • Atherosclerosis susceptibility [7]
  • Intracranial aneurysm [8]
  • Periodontitis [7]

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. [9] 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
  • Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

References

  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).
  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.
  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.
  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.
  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.
  6. 6.0 6.1 Wan G, Mathur R, Hu X, et al. Long non-coding RNA ANRIL (CDKN2B-AS) is induced by the ATM-E2F1 signaling pathway[J]. Cell Signal, 2013, 25: 1086-1095.
  7. 7.0 7.1 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.
  8. 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.
  9. 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 ATCACCATAG TGAACATGTA ATGCTTACCT AGTGCCAGAT 003600
003601 GCTGTCTAGG CATTTTACAT GTGTTACTGG TAACTCATGT AATCCTCATA ACAACCTTAT AAGGTGGTTG CTATTATCCC 003680
003681 CATGTTACAT ATGAAGAGAC AGAAGCATAA AGAAGTTGCA CCGCTGGTAA TTGGCTGGGA TTTGAACTTA AGCAGTCTAA 003760
003761 CCTTAGAGTA ATGATTTTAA CAACTATGCT ATATACATAC AAATTTACAA AATAAAACTG GGCTCAGACA ATAAAAAAAA 003840
003841 AAAAAAAAAA AAAAAAA