NORAD

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NORAD preserves genomic stability.

NORAD, is characterized mammalian long non-coding RNA, serves as a major regulator of PUM gene activity in human cells.

Annotated Information

Approved Symbol

NORAD

Approved Name

NORAD: Non-coding RNA activated by DNA damage (HGNC nomenclature) LINC00657[1]

Characteristics

NORAD gene is one-exontranscript and is mapped to chromosome 20q11.23 based on an alignment of the NORAD sequence (GenBank AI619767) with the genomic sequence (GRCh38).[2]

NORAD is a polyadenylated 5.3 kbps lncRNA with low protein-coding potential, based on homology with its mouse ortholog.[1]


NORAD has 5 tandem repeats of an approximately 400-nucleotide NORAD domain (ND) and 15 copies of the Pumilio response element (PRE).[1]


RNA FISH demonstrated nearly exclusive cytoplasmic localization of NORAD RNA.[1]


NORAD locus depicts mammalian conservation and has features of an RNA polymerase II transcription unit including an enrichement of H3K4me3 modified histones at a transcription start site. [3].

Function

NORAD preserves genomic stability by acting as multivalent binding platforms for PUMILIO family of RNA binding proteins.[1]

Chromosomal instability is specifically due to NORAD loss of function.[4]

Conditional knockout or knockdown of NORAD expression caused multiple mitotic errors, including anaphase bridges, mitotic slippage, and significant aneuploidy. [1].

NORAD upregulates transforming growth factor-beta (TGF-beta) signalling and regulates TGF-beta-induced epithelial-to-mesenchymal transition (EMT)-like phenotype. [5]

NORAD Act as a miR-590-3p Sponge to Facilitate Low Concentration Oxidized Low-Density Lipoprotein-Induced Angiogenesis.[6]

NORAD enhances the hypoxia-induced epithelial-mesenchymal transition to promote metastasis in pancreatic cancer. [7].

Expression

NORAD gene expression is responsible for regulation of PUMILIO protein activity which is directly involved in maintaining chromosomal stability [1].

NORAD regulates the chromosomal stability by controlling the activity of PUMILIO.[1]

RNA sequence data indicated that NORAD was expressed in all human tissues, with highest expression in brain, and lowest expression in liver and lymph node. Absolute copy number analysis in human cell lines revealed that NORAD was present at approximately 300 to 1,400 copies per cell. [2]

Regulation

p35 is found to be indirectly regulating the expression of lncrna NORAD [8]

Diseases

  • pancreatic cancer [7]
  • bladder cancer [9]
  • esophageal squamous cell carcinoma [10]

Labs working on this lncRNA

  • Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.[3]
  • Center for Biomolecular Science and Engineering, CBSE, UC Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA. [4]
  • Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel. [8]
  • Center for Applied Medical Research, University of Navarra, 55 Pio XII Avenue, 31008 Pamplona, Spain. [5]
  • Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. [6]

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Lee S, Kopp F, Chang TC, Sataluri A, Chen BB, Sivakumar S et al. Noncoding RNA NORAD Regulates Genomic Stability by Sequestering PUMILIO Proteins[J]. Cell. 2016, 164(1-2):69-80.
  2. 2.0 2.1 Hartz, P. A. Personal Communication. Baltimore, Md. 7/14/2016.
  3. 3.0 3.1 Rosenbloom KR, Armstrong J, Barber GP, Casper J, Clawson H, Diekhans M et al. The UCSC Genome Browser database: 2015 update[J]. Nucleic acids research. 2015, 43(Database issue):D670-681.
  4. 4.0 4.1 Tichon A, Gil N, Lubelsky Y, Havkin Solomon T, Lemze D, Itzkovitz S et al. A conserved abundant cytoplasmic long noncoding RNA modulates repression by Pumilio proteins in human cells[J]. Nature communications. 2016.
  5. 5.0 5.1 Kawasaki N, Miwa T, Hokari S, Sakurai T, Ohmori K, Miyauchi K et al. Long noncoding RNA NORAD regulates transforming growth factor-ß signaling and epithelial-to-mesenchymal transition-like phenotype[J]. Cancer science. 2018, 109(7):2211.
  6. 6.0 6.1 Bao M-h, Li G-y, Huang X-s, Tang L, Dong L-p & Li J-m. Long non-coding RNA LINC00657 acting as miR-590-3p sponge to facilitate low concentration oxidized low-density lipoprotein-induced angiogenesis[J]. Molecular pharmacology. 2018,mol. 117.110650.
  7. 7.0 7.1 Bao M-h, Li G-y, Huang X-s, Tang L, Dong L-p & Li J-m. Long non-coding RNA LINC00657 acting as miR-590-3p sponge to facilitate low concentration oxidized low-density lipoprotein-induced angiogenesis[J]. Molecular pharmacology. 2018,mol. 117.110650.
  8. 8.0 8.1 Sanchez Y, Segura V, Marin-Bejar O, Athie A, Marchese FP, Gonzalez J et al. Genome-wide analysis of the human p53 transcriptional network unveils a lncRNA tumour suppressor signature[J]. Nature communications. 2014.
  9. Li Q, Li C, Chen J, Liu P, Cui Y, Zhou X et al. in Urologic Oncology: Seminars and Original Investigations. 310. e315-310. e322 (Elsevier).
  10. Wu X, Lim Z-F, Li Z, Gu L, Ma W, Zhou Q et al. NORAD expression is associated with adverse prognosis in esophageal squamous cell carcinoma[J]. Oncology research and treatment. 2017, 40(6):370-374.

Sequence

>gi|647979|ref|NR_027451.1| Homo sapiens non-coding RNA activated by DNA damage (NORAD), long non-coding RNA

000001 AGTTCCGGTC CGGCAGAGAT CGCGGAGAGA CGCAGAACGC AGCCCGCTCC TCCAGGGCCC TCCAGGCCCT CCGGCCCCGG 000080
000081 GCCGGCGGGT GAACTGGGGG GCCCCGGGAC AGGCCGAGCC CTCTGCCCTG CAGATAACGG AGGCCTCTGC TGTGGCTGCC 000160
000161 CACTGGCTGT GCCCGCCCAC TGGCTGTGCC CAGACCTTGA AGCCGCAGCG AACCTCTCTT TCCCACCCCA CCTCGGTGAC 000240
000241 TAATGGCGGC CGTGGCGTCT CCCAGCCCGG ACCCCGCCGG CACCCGGGTC TCCCGACCCA AGCCTCGACG AAACCCCCGC 000320
000321 AGAGCCGCCG GGACGCAGCG CCTTTGGGCG GCGCTGGGCG TGGTGGGCCG GGAAGTATGG CGGCAGCTCG AACGCCGCGC 000400
000401 GGCGGAGGCC ATTAAGGCGT GGACGGCCCG GGAAGGCGGC CTAGGGACGC AAGCAGGCTC GGCCGCCTCT TTAGGCCACG 000480
000481 GAGCCGCGCA GATCCGGTTC CCGGGTGACC ACTCTGTCGC CATTGGGCGA GACCTACCTA GTCCTGACGA CAACGGACAA 000560
000561 AGGCCTTAAG GGGCCTGGAA GGTGAGCGAA GTCCCGAACG ACGACGGGTG GAACGGTTAG CGGCCATCGG GCGGTTGGTC 000640
000641 TTCATTCTAC CAGACTTTGC TGTCGGAAGA GAGAAATGGT AGAATGACAG GCCACGTTTG GCCCGTTGGA AATGCCCACC 000720
000721 ACCCTCTGGG AAGATTTACT GGCCGTTTAT GGAAGGCCTG TGTATATAAT ATGAAAAAGC TGCTCTCAAC TCCACCCCAA 000800
000801 CCTTTTAATA GAAAACATTT GTCACATCTA GCCCTTCTAG ATGGAAAGAG GTTGCCGACG TATGATAAAA TAGAGTTAGA 000880
000881 AAGTTACACA TCTTGTAAAT TCTCATTTGT TTAAAAGAAA TCATAGAAAA TACATGTCTT CTGGAGATGA CTTTTGGAAA 000960
000961 TGGAGTTGTT AAGACGGCCT CTGGAAGCGA TACGTCCACG TTTGTTAAGT GGGTTAGATG ACATGGAGCT GGAAGACCTG 001040
001041 AGAAGGAAGA GAAGAAGGTT CTATGCTAGA CTGGTCATAT TTAGAAGACA TTTTCATATT CTATCCATTG TTTTGTGTGC 001120
001121 ATTTTATTCC TCACTACTGT GTATATAGTT GACAATGCTA AGCTTTTTTG AAATGTCTCT TCTTTTTAGA TGTTCTGAAG 001200
001201 TGCCTGATAT GTTAAAATTA GAGGTAGCAA AATCACATTT TGTAAATACC TTTTTGTTAC AATTCATAGG AAATATTTTT 001280
001281 GGGGGGGAAT GGCCAAATCA CCTGTTGAGT AATACTCATT GTGTTTGTGC AGTGGTTCAG GGGAGGAGAG AGGAGGGGGA 001360
001361 GGTGCAGAGA GCTCTATGCC ATCCTGTTTA CAGCGAGGCA AGATGAATCA TTATGTCTGT GCATTTTGTT TTACTTATCT 001440
001441 GTGTATATAG TGTACATAAA GGACAGACGA GTCCTAATTG ACAACATCTA GTCTTTCTGG ATGTTAAAGA GGTTGCCAGT 001520
001521 GTATGACAAA AGTAGAGTTA GTAAACTAAT ATATTTTGTA CATTTTGTTT TACAAGTCCT AGGAAAGATT GTCTTCTGAA 001600
001601 AATTTGATGT CTTCTGGGTT GATGGAGATG GGAAGGGTTC TAGGCCAGAA TGTTCACATT TGGAAGACTC TTTCAAATTA 001680
001681 TAACTGTTGT TACATGTTTG CAGTTTATTC AAGACTGCTG TATACATAGT AGACAAATTA ACTCCTTACT TGAAACATCT 001760
001761 AGTCTATCTA GATGTTTAGA AGTGCCCGAT GTATGTTAAA TGTATAGGTA GTAAAATACC ACTTTGTAAA TATCTTTTTG 001840
001841 CTAAAATTCA TAGGAAATGC TTTTGGAAAT TGAATTGTGA AGCCACCTTT GTGAACAGTA TAGTAATGTC TATACTTGTT 001920
001921 CAATAGTTTA GAGGAGGTAG GAGGGAAGAA ATTGCAAAAG GTAATATTAC TAGTGTGTTC ATACTTGGAC ATTTTCAGAC 002000
002001 ACCATTTTTC TATATGTTTT GTGCATTTTG TTTTGCTCTG TATATAGTAT ATATAATGGA CAAATAGTCC TAATTTTTCA 002080
002081 ACATCTAGTC TCTAGATGTT AAAGAGGTTG CCAGTGTATG ACAAAGGAGT AAAATTAGCA TATTTTGTAC ACTTTGTGTT 002160
002161 GAAATTCGTA GGAAAACTTG TCTTCTGTAA AGACTTTTGC ATAGGAATTT GTTTGACCAT CTCTAAGCAT TACACGTGCC 002240
002241 TGTACTTGTC CACTGGATTG AAGGCAGAGA AGGAAGGGAG GAGGGAATGA TTCAAGGCCA AAATGGCCAC ATTTAGAAGA 002320
002321 TACCTCAGAT GATAACCATT GTTATGTGTG TGCAATTTTA TTTAACAGTG CTGTGTATGT GGTGGACAAG TTATATGAAA 002400
002401 TATCTAGTCT TTCTAGATAT TTGGAAGTGC TTGATGTATT TAAAAGTGGT AGTAGAATAA CACTTTGTAA ATAGCTTTTA 002480
002481 AAAACTGATG GGAAATGCTG TTTGGAAGTG GAATTGTTGA ACCACCTGGG AGGTGGGAGG GAAGAAATTG CAAATGGTGT 002560
002561 TTTGCCATTG TTTATTAGAA AATTTCAGCT TAATCCATTG TGTATATGTT ACATGCATTT CATTTAACTT TGCTATACTG 002640
002641 TATATATTGT ATATATAACG GACAAATTAG TCCCGATTTT ATAATATCTA GTCTCTAGAT ATTAAAGAGG TTGCCAATGT 002720
002721 ATGACAGAAG TAGAGTTAGT AAACTAACAC ATTTTGTACA CTTTGTTAAA ATTTGTAGAA AGGCTGTCTT CTGAAAAGGA 002800
002801 CTTTTGGAAG TGAGATAACA TCAGCTCTAA GTGACACGTG CCTATATCCA TCAGGTTGGT GGTGGAGAGG AGTTGGAAGG 002880
002881 AATGAAGGGT TCTAGACCAG AATGTTCGTA TTTAGAAGAC ACTATCAGAT ATAACCATTG TTACATGTGT GTAGTTTATT 002960
002961 CAACCCTACT GTGTATATAG CGGACAAACT TAAGTCCTTA TTTGAAACAT CTAGTCTTTC TAGATGTTTA GAAGTGCACA 003040
003041 AAGTATGTTA AAAGTAGAGG TAGTAAATAA CACATTTTGT AGCTATCCTT TTGATATGAA ATATTGTCTT GGAAATTGAT 003120
003121 CAATTCTCTG AGCAGTACCC ATTTTGATAT TTGTGCTGGT TCAGGGGGAA GGAGGAGCAC AAAGTGCAAA GGGCTTTCTA 003200
003201 CCAGTGTCCA GTGTGTTTAT GAGGAGGCAC ATTGACCATT GTCCCTTATG TCTGCATTTT CATTTACTGT GCTGTGTATA 003280
003281 TAGTGTATAT AAGCGGACAT AGGAGTCCTA ATTTACGTCT AGTCGATGTT AAAAAGGTTG CCAGTATATG ACAAAAGTAG 003360
003361 AATTAGTAAA CTACTACATT GAGTACACTT TGTGTTAAAA TTCATAGGGA AGACTTCTTA AAAACAAGTG AAATTGTTAA 003440
003441 AACCCCCCCT AAGCATTACA GATGGCTTAT AGCTGTCCAC GGGGTTGGTA GAGGTGGGAA AGGGAAGGGT TCTAGGCCAG 003520
003521 AATGTTCCTA TTTAGAAGAC ACTCAAATTA CAGTCTGTGT TATGTATGTA TACCATTTAT TCAATGCTAC TGTGTATATA 003600
003601 ATGGAAAACT TAAGTCCAGT TTGAAACATC TAGTCTTTCT AGGTGTTTAA AAGTGTACAA CGGCCTGTCG CAGTGGCGCA 003680
003681 TGCCTGTAAT CCCAGCACTT TGGGAGGCCG AGGCAGGCGG ATCACGAGGT CAAGAGATCA GGACCATCTT GGCCAACATG 003760
003761 GTGAAACCCC ATCTTTACTA AAAATACAAA AATTAGCTGG TCGTGGTGGT GCCCACCTGT AGCCCCAGTT ACTCGAGAGG 003840
003841 CTGAGGCAGG AGAATCGCTT GAACTTGGGA GGCGGAAGTT GCAGTGAGCC AAGATCGCAC CACTGCACTC CAGCCTGGCG 003920
003921 ACAGAGCGAG GCTCCGTTTC AAAAAAAAAA GTGCACAATG TAGGTTAACA GTAGAGGGCT TAAGTAACAC CCCTCTAAGC 004000
004001 ATTTGTTTTC AGTACTTCCT AGGAGTGGTT GCATTTGGGA ATGGAATTGT TAAAACTTGA TGCTTAGGAG CGAATGCAGA 004080
004081 CTATTCATTG GGTGTTTGGG GTGGGGGAAG GGGGGGTGGG CAGAGGAGGT ATGCAGGGAG AGGGGTTCTG TGCTCCTGAG 004160
004161 ATTAGTTCAG ATGGTCTAAC CATTGTTCTA TATGTGCATT TTAGTTAATA TTGTGTATTA AAGGATAAGT CTTAATGCTC 004240
004241 AAAGTATGTT AAAAATAGAT GTAGTAAATC AGTCCCTTTG TGAATGTCCT TTTGTTAGTT TTTAGGAAGG CCTGTCCTCT 004320
004321 GGGAGTGACC TTTATTAGTC CACCCCTTGG AGCTAGACAT CCTGTACTTA GTCACGGGGA TGGTGGAAGA GGGAGAAGAG 004400
004401 GAAGGGTGAA GGGAAGGGCT CTTTGCTAGT ATCTCCATAT CTAGACGATG GTTTTAGATG ATAACCACAG GTCTACAAGA 004480
004481 GCGTTTTTAG TAAAGTGCCT GTGTTCATTG TGGACAAAGT TATTATTTTG CAACATCTAA GCTTTACGAA TGGGGTGACA 004560
004561 ACTTATGATA AAAACTAGAG CTAGTGAATT AGCCTATTTG TAAATACCTT TGTTATAATT GATAGGATAC ATCTTGGACA 004640
004641 TGGAATTGTT AAGCCACCTC TGAGCAGTGT ATGTCAGGAC TTGTTCATTA GGTTGGCAGC AGAGGGGCAG AAGGAATTAT 004720
004721 ACAGGTAGAG ATGTATGCAG ATGTGTCCAT ATATGTCCAT ATTTACATTT TGATAGCCAT TGATGTATGC ATCTCTTGGC 004800
004801 TGTACTATAA GAACACATTA ATTCAATGGA AATACACTTT GCTAATATTT TAATGGTATA GATCTGCTAA TGAATTCTCT 004880
004881 TAAAAACATA CTGTATTCTG TTGCTGTGTG TTTCATTTTA AATTGAGCAT TAAGGGAATG CAGCATTTAA ATCAGAACTC 004960
004961 TGCCAATGCT TTTATCTAGA GGCGTGTTGC CATTTTTGTC TTATATGAAA TTTCTGTCCC AAGAAAGGCA GGATTACATC 005040
005041 TTTTTTTTTT TTTTTAGCAG TTTGAGTTGG TGTAGTGTAT TCTTGGTTAT CAGAATACTC ATATAGCTTT GGGATTTTGA 005120
005121 ATTGGTAAAT ATTCATGATG TGTGAAAAAT CATGATACAT ACTGTACAGT CTCAGTCCCA TAAAATTGGA TGTTGTGCCT 005200
005201 ACACACAGGA TCTAGAAGAA TATGTCAAAC TATAAACTGC TTGTGATTGT GAATGACTTT GTTCTTTGCT TGTGTTTTTC 005280
005281 AATTTCCTAT AATGCACATA CTAACTTTTA AAAAATAAAG GTTATTTTAA AAGCCTGTAT TAAAAAAAAA AAAAAAAAAA 005360
005361 AAAAAAAAAA AAAAAAAA