NORAD

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NORAD, non-coding RNA activated by DNA damage, has a critical role in maintaining genomic stability.

Annotated Information

Approved Symbol

NORAD

Approved Name

non-coding RNA activated by DNA damage

Synonyms

LINC00657, LOC647979

Chromosome

20q11.23

RefSeq ID

NR_027451

Ensembl ID

ENSG00000260032

Characteristics

Characterization of NORAD, a highly abundant, conserved mammalian noncoding RNA induced by DNA damage [1].

NORAD is a highly abundant(expressed at 500‐1000 copies per cell), conserved mammalian noncoding RNA induced by DNA damage[1]. Deletion of this lncRNA induces chromosomal instability and aneuploidy[2].

NORAD produces a 5.3 kb transcript that does not overlap other genes, starts from a single strong promoter overlapping a CpG island, terminates with a single major canonical poly(A) site, but is unspliced[3]. Unlike most lncRNAs,it contains at least 12 structured repeated units and highly conserved consensus binding sites for an RNA-binding protein (RBP), and that is required for proper regulation of the RBP targets at physiological levels [3].

Expression

NORAD expression was increased in CC [4].
NORAD modulates RBMX and is essential for assembly of a topoisomerase complex [2].

NORAD is upregulated in many cancers, including breast cancer[5], esophageal squamous cell carcinoma (ESCC)[6], pancreatic cancer[7], colorectal cancer (CRC)[8], bladder cancer (BC)[9], and cervical cancer (CC)[4].

Function

NORAD, non-coding RNA activated by DNA damage, has a critical role in maintaining genomic stability[1][10][2]. NORAD maintains both ploidy and chromosomal stability by sequestering PUMILIO proteins, which repress key mitotic, DNA repair, and DNA replication factors to repress the stability and translation of mRNAs to which they bind[1]. NORAD is unusually abundant with expression in the range of ~500–1000 copies per cell in human cell lines, and the presence of at least 15 PUMLIIO response elements (PREs) per NORAD transcript further amplifies, by more than an order of magnitude, the number of competitive binding sites provided by this lncRNA, this strongly support its function as a bona fide molecular decoy[1]. Also, multiple lines of evidence indicate that NORAD affects genomic stability through its direct interaction with Pumilio2 (PUM2) and possibly Pumilio 1 (PUM1),which are known to bind to the 3′UTR of target mRNAs via an 8-nt specific sequence and reduce their stability[10]. In addition, NORAD is essential for the assembly of the ribonucleoprotein complex NARC1 and NORAD assembles a topoisomerase complex critical for genome stability[2].

NORAD is an oncogenic lncRNA[5]. Increased NORAD expression might serve as a novel molecular predictor of poor prognosis in ESCC patients and maybe a potential target for diagnosis and gene therapy[6], and high NORAD expression could serve as an independent prognostic factor for overall survival of patients with transitional BC[9].

It is found that NORAD functions as a ceRNA through competition for miR-125a-3p to play the oncogenic role in the pathogenesis of pancreatic cancer[7], inhibition of miR-202-5p to promote colorectal cancer progression[8], modulating miR-590-3p/SIP1 axis in colorectal cancer[4].

Also, NORAD upregulates transforming growth factor-β (TGF-β) signaling and regulates TGF-β-induced epithelial-to-mesenchymal transition (EMT)-like phenotype, which is a critical step in the progression of lung adenocarcinoma, A549 cells[11].

Disease

  • bladder cancer[9]
  • breast cancer[5]
  • cervical cancer[4]
  • colorectal cancer[8]
  • esophageal squamous cell carcinoma[6]
  • pancreatic cancer[7]

Sequence

>gi|226246632|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

Labs working on this lncRNA

  • Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.[1]
  • Pathobiology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.[1]
  • Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.[5]
  • Department of Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.[5]
  • Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, USA.[10]
  • State Key Laboratory of Oncology in South China & Collaborative Innovation Center for Cancer Medicine,Sun Yat-sen University Cancer Center, Guangzhou, China.[6]
  • Department of Oncology, Guizhou Provincial People’s Hospital, Guiyang, China.[6]
  • Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.[7]
  • Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.[7]
  • The First Department of General Surgery, Linyi Central Hospital, No. 17 Yishui County, Linyi 276400, Shandong Province, China.[8]
  • The First Department of Endocrinology, Linyi Central Hospital, No. 17 Yishui County, Linyi 276400, Shandong Province, China.[8]
  • Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan Province, PR China.[9]
  • Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.[11]
  • Department of Respiratory Medicine and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.[11]
  • Department of Obstetrics and Gynecology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China.[4]
  • Department of Surgery, Kaifeng University, Kaifeng 475000, Henan Province, China.[4]
  • Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.[3]
  • Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.[3]
  • Broad Institute of MIT and Harvard, Cambridge, MA, USA.[2]
  • Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.[2]

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Lee S, Kopp F, Chang TC, Sataluri A, Chen B, Sivakumar S, et al. Noncoding RNA NORAD Regulates Genomic Stability by Sequestering PUMILIO Proteins. Cell. 2016;164(1-2):69-80.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 Munschauer M, Nguyen CT, Sirokman K, Hartigan CR, Hogstrom L, Engreitz JM, et al. The NORAD lncRNA assembles a topoisomerase complex critical for genome stability. Nature. 2018.
  3. 3.0 3.1 3.2 3.3 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. Nature communications. 2016;7:12209.
  4. 4.0 4.1 4.2 4.3 4.4 4.5 Huo H, Tian J, Wang R, Li Y, Qu C, Wang N. Long non-coding RNA NORAD upregulate SIP1 expression to promote cell proliferation and invasion in cervical cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2018;106:1454-60.
  5. 5.0 5.1 5.2 5.3 5.4 Liu H, Li J, Koirala P, Ding X, Chen B, Wang Y, et al. Long non-coding RNAs as prognostic markers in human breast cancer. Oncotarget. 2016;7(15):20584-96.
  6. 6.0 6.1 6.2 6.3 6.4 Wu X, Lim ZF, Li Z, Gu L, Ma W, Zhou Q, et al. NORAD Expression Is Associated with Adverse Prognosis in Esophageal Squamous Cell Carcinoma. Oncology research and treatment. 2017;40(6):370-4.
  7. 7.0 7.1 7.2 7.3 7.4 Li H, Wang X, Wen C, Huo Z, Wang W, Zhan Q, et al. Long noncoding RNA NORAD, a novel competing endogenous RNA, enhances the hypoxia-induced epithelial-mesenchymal transition to promote metastasis in pancreatic cancer. Molecular cancer. 2017;16(1):169.
  8. 8.0 8.1 8.2 8.3 8.4 Zhang J, Li XY, Hu P, Ding YS. LncRNA NORAD contributes to colorectal cancer progression by inhibition of miR-202-5p. Oncology research. 2018.
  9. 9.0 9.1 9.2 9.3 Li Q, Li C, Chen J, Liu P, Cui Y, Zhou X, et al. High expression of long noncoding RNA NORAD indicates a poor prognosis and promotes clinical progression and metastasis in bladder cancer. Urologic oncology. 2018;36(6):310 e15- e22.
  10. 10.0 10.1 10.2 Ventura A. NORAD: Defender of the Genome. Trends in genetics : TIG. 2016;32(7):390-2.
  11. 11.0 11.1 11.2 Kawasaki N, Miwa T, Hokari S, Sakurai T, Ohmori K, Miyauchi K, et al. Long noncoding RNA NORAD regulates transforming growth factor-beta signaling and epithelial-to-mesenchymal transition-like phenotype. Cancer science. 2018;109(7):2211-20.