NONHSAT007663

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GAS5, functions as a ceRNA to regulate hZIP1

Annotated Information

Annotated Symbol

GAS5

Annotated Name

GAS5: Growth Arrest Specific 5

Characteristics

GAS5 the Growth arrest-specific transcript , multiple splice isoforms of ~250, ~450, ~600nuc and longer, encodes 9 (10 in humans) snoRNAs in its introns. [1][2][3][4]

Function

GAS5 is necessary and sufficient for growth arrest in human peripheral blood T-cells. It functions by controlling apoptosis and the cell cycle in lymphocytes [3]. In some cell lines certain GAS5 isoforms act to sensitise the cells to apoptosis but can't induce apoptosis on their own. In other cells types Gas5 can both induce apoptosis and growth arrest and sensitise the cells to further apoptosis [5]. GAS5 carries out its function by binding the DNA binding domain of the glucocorticoid receptor (GR) with a sequence that mimmics the glucocorticoid response element (GRE). GAS5 is translocated into the nucleus bound to the GR where it prevents GR from binding GREs and regulating transcription of target genes including apoptosis inhibitors [6]. GAS5 also appears to repress the action of many steroid hormone receptors, showing some similarities to another lncRNA SRA [6]. GAS5 is a snoRNA host and a functional RNA. Function does not require putative but nonconserved ORF, or the intronic snoRNAs [5][7][6].

Regulation

GAS5 can be regulated by mTOR, with mTOR (which promotes cellular proliferation) acting to inhibit the function of GAS5 [7]. Expression of GAS5 mRNA is regulated at the posttranscriptional level during growth and at the transcriptional level in differentiated cells [2].

Disease

  • Autoimmune disease [7]
  • B-cell neoplasms [7]
  • Breast cancer [5]
  • Kidney cancer [7]
  • Lymphoma [7]
  • Prostate cancer melanoma [7]
  • Systemic lupus erythaematosus [7]

Expression

GAS5 is widely expressed in adult tissues and over embryonic development [1]. Transcript undergoes post-transcriptional regulation, highly unstable but stabilised by growth arrest, serum starvation and inhibition of protein synthesis [2][4][6]. Associates with ribosomes in the cytoplasm [4]. Localises to both the nucleus and the cytoplasm [6]. Down-regulated in breast cancer [5]. Transcript was classified as unstable with a half-life >4 hr in human Hela cells [8].

Labs working on this lncRNA

  • European Molecular Biology Laboratory, Heidelberg, Germany
  • Institute for Science and Technology in Medicine and School of Life Sciences, Huxley Building, Keele University, Keele, United Kingdom
  • King's College London, Department of Haematological Medicine, The Rayne Institute, London, United Kingdom (F.F.)

References

  1. ↑ 1.0 1.1 Schneider C, King RM & Philipson L. Genes Specifically Expressed at Growth Arrest of Mammalian-Cells[J]. Cell. 1988, 54(6):787-793.
  2. ↑ 2.0 2.1 2.2 Coccia EM, Cicala C, Charlesworth A, Ciccarelli C, Rossi GB, Philipson L et al. Regulation and Expression of a Growth Arrest-Specific Gene (Gas5) during Growth, Differentiation, and Development[J]. Mol Cell Biol. 1992, 12(8):3514-3521.
  3. ↑ 3.0 3.1 Mourtada-Maarabouni M, Hedge VL, Kirkham L, Farzaneh F & Williams GT. Growth arrest in human T-cells is controlled by the non-coding RNA growth-arrest-specific transcript 5 (GAS5)[J]. J Cell Sci. 2008, 121(7):939-946
  4. ↑ 4.0 4.1 4.2 Smith CM & Steitz JA. Classification of gas5 as a multi-small-nucleolar-RNA (snoRNA) host gene and a member of the 5 '-terminal oligopyrimidine gene family reveals common features of snoRNA host genes[J]. Mol Cell Biol. 1998, 18(12):6897-6909
  5. ↑ 5.0 5.1 5.2 5.3 Mourtada-Maarabouni M, Pickard MR, Hedge VL, Farzaneh F & Williams GT. GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer[J]. Oncogene. 2009, 28(2):195-208.
  6. ↑ 6.0 6.1 6.2 6.3 6.4 Kino T, Hurt DE, Ichijo T, Nader N & Chrousos GP. Noncoding RNA Gas5 Is a Growth Arrest- and Starvation-Associated Repressor of the Glucocorticoid Receptor[J]. Sci Signal. 2010, 3(107).
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 Mourtada-Maarabouni M, Hasan AM, Farzaneh F & Williams GT. Inhibition of Human T-Cell Proliferation by Mammalian Target of Rapamycin (mTOR) Antagonists Requires Noncoding RNA Growth-Arrest-Specific Transcript 5 (GAS5)[J]. Mol Pharmacol. 2010, 78(1):19-28.
  8. ↑ 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 noncoding transcripts in mammals[J]. Genome Res. 2012, 22(5):947-956

Sequence

>gi|60674|ref|NR_002578.3| Homo sapiens growth arrest specific 5 (GAS5), transcript variant 1, long non-coding RNA

000001 GTCTTTTCGA GGTAGGAGTC GACTCCTGTG AGGTATGGTG CTGGGTGCAG ATGCAGTGTG GCTCTGGATA GCACCTTATG 000080
000081 GACAGTTGTG TCCCCAAGGA AGGATGAGAA TAGCTACTGA AGTCCTAAAG AGCAAGCCTA ACTCAAGCCA TTGGCACACA 000160
000161 GGCATTAGAC AGAAAGCTGG AAGTTGAAAT GGTGGAGTCC AACTTGCCTG GACCAGCTTA ATGGTTCTGC TCCTGGTAAC 000240
000241 GTTTTTATCC ATGGATGACT TGCTTGGGTA AGGACATGAA GACAGTTCCT GTCATACCTT TTAAAGGTAT GGAGAGTCGG 000320
000321 CTTGACTACA CTGTGTGGAG CAAGTTTTAA AGAAGCAAAG GACTCAGAAT TCATGATTGA AGAAATGCAG GCAGACCTGT 000400
000401 TATCCTAAAC TAGGGTTTTT AATGACCACA ACAAGCAAGC ATGCAGCTTA CTGCTTGAAA GGGTCTTGCC TCACCCAAGC 000480
000481 TAGAGTGCAG TGGCCTTTGA AGCTTACTAC AGCCTCAAAC TTCTGGGCTC AAGTGATCCT CAGCCTCCCA GTGGTCTTTG 000560
000561 TAGACTGCCT GATGGAGTCT CATGGCACAA GAAGATTAAA ACAGTGTCTC CAATTTTAAT AAATTTTTGC AATCCATCAA 000640
000641 AAAAAAAAAA AAAAAA
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