Difference between revisions of "NONHSAT007663"

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Please input one-sentence summary here.
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''GAS5'', functions as a ceRNA to regulate hZIP1
  
 
==Annotated Information==
 
==Annotated Information==
 
===Name===
 
===Name===
GAS5
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Approved symbol: ''GAS5''
  
===Characteristics===
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Approved name: ''GAS5'': growth arrest specific 5
Growth arrest-specific transcript [http://www.ncbi.nlm.nih.gov/pubmed/3409319 (Schneider (1988))], multiple splice isoforms [http://www.ncbi.nlm.nih.gov/pubmed/1630459 (Coccia (1992))] of ~250, ~450, ~600nuc and longer [http://www.ncbi.nlm.nih.gov/pubmed/18354083 (Mourtada-Maarabouni (2008))], encodes 9 (10 in humans) snoRNAs in its introns [http://www.ncbi.nlm.nih.gov/pubmed/9819378 (Smith (1998))].
 
  
===Function===
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Alias symbols: SNHG2, NCRNA00030
Necessary and sufficient for growth arrest in human peripheral blood T-cells. Functions by  controlling apoptosis and the cell cycle in lymphocytes [http://www.ncbi.nlm.nih.gov/pubmed/18354083 (Mourtada-Maarabouni (2008))]. 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 [http://www.ncbi.nlm.nih.gov/pubmed/18836484 (Mourtada-Maarabouni (2009))]. Gas5 can be regulated by mTOR, with mTOR (which promotes cellular proliferation) acting to inhibit the function of Gas5 [http://www.ncbi.nlm.nih.gov/pubmed/20421347 (Mourtada-Maarabouni (2010))]. 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 [http://www.ncbi.nlm.nih.gov/pubmed/20124551 (Kino (2010))]. Gas5 also appears to repress the action of many steroid hormone receptors, showing some similarities to another lncRNA SRA [http://www.ncbi.nlm.nih.gov/pubmed/20124551 (Kino (2010))]. Gas5 is a snoRNA host and a functional RNA. Function does not require putative but nonconserved ORF, or the intronic snoRNAs ([http://www.ncbi.nlm.nih.gov/pubmed/18354083 Mourtada-Maarabouni (2008)], [http://www.ncbi.nlm.nih.gov/pubmed/18836484 Mourtada-Maarabouni (2009)], [http://www.ncbi.nlm.nih.gov/pubmed/20124551 Kino (2010)]).
 
  
===Expression===
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HGNC ID: HGNC: 16355
Widely expressed in adult tissues and over embryonic development [http://www.ncbi.nlm.nih.gov/pubmed/1630459 (Coccia (1992))]. Transcript undergoes post-transcriptional regulation, highly unstable but stabilised by growth arrest, serum starvation and inhibition of protein synthesis ([http://www.ncbi.nlm.nih.gov/pubmed/1630459 Coccia (1992)], [http://www.ncbi.nlm.nih.gov/pubmed/9819378 Smith (1998)], [http://www.ncbi.nlm.nih.gov/pubmed/20124551 Kino (2010)]). Associates with ribosomes in the cytoplasm [http://www.ncbi.nlm.nih.gov/pubmed/9819378 (Smith (1998))]. Localises to both the nucleus and the cytoplasm (Kino (2010))]. Down-regulated in breast cancer [http://www.ncbi.nlm.nih.gov/pubmed/18836484 (Mourtada-Maarabouni (2009))]. Transcript was classified as unstable with a half-life >4 hr in human Hela cells [http://www.ncbi.nlm.nih.gov/pubmed/22369889 (Tani (2012))]. Similar half-lives were identified in human B cells and mouse 3T3 fibroblasts ([http://www.ncbi.nlm.nih.gov/pubmed/19561200 Friedel (2009)], [http://www.ncbi.nlm.nih.gov/pubmed/22406755 Clark (2012)]).
 
  
===Conservation===
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LncBook ID: HSALNT0017702
Gas5 in mouse and human do not show high sequence identity [http://www.ncbi.nlm.nih.gov/pubmed/17468437 (Tanaka-Fujita (2007))] although the GRE mimmic region is conserved [http://www.ncbi.nlm.nih.gov/pubmed/20124551 (Kino (2010))]. Most of the snoRNAs found in human Gas5 also cluster in the same order in a putatively noncoding RNA host gene in chicken. 42% homology was found between human Gas5 and the chicken gene which was named Gas5-like [http://www.ncbi.nlm.nih.gov/pubmed/19232134 (Shao (2009))].
 
  
===Misc===
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Ensembl ID: ENSG00000234741
Mourtada-Maarabouni., et al (2010) provide an interesting hypothesis for how Gas5 levels and therefore function is regulated. - Gas5 is stabilised by inhibition of protein synthesis suggesting it may normally be a target for nonsense mediated decay (NMD). mTOR regulates 5' TOP genes (which includes Gas5) promoting translation, whereas mTOR inhibition inhibits translation. This could allow mTOR to inhibit Gas5 by promoting Gas5 NMD. This suggests that since Gas5 is known to be functional at the RNA level, any Gas5 translation may be a regulatory to control Gas5 levels and not necessarily to produce a functional protein.
 
  
===Transcriptomic Nomeclature===
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RefSeq ID: NR_002578
Please input transcriptomic nomeclature information here.
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===Characteristics===
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''GAS5'' the Growth arrest-specific transcript , multiple splice isoforms of ~250, ~450, ~600nuc and longer, encodes 9 (10 in humans) snoRNAs in its introns. <ref name="ref1" /><ref name="ref2" /><ref name="ref3" /><ref name="ref4" />
  
===Regulation===
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''GAS5'' is one of the lncRNAs in a six-lncRNA signature that is independently associated with the prognosis of GBM patients<ref name="ref9"/>.  
Please input regulation information here.
 
  
===Allelic Information and Variation===
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===Function===
Please input allelic information and variation information here.
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''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 <ref name="ref3" />.
 +
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 <ref name="ref5" />.
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''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 <ref name="ref7" />.
 +
''GAS5'' also appears to repress the action of many steroid hormone receptors, showing some similarities to another lncRNA SRA <ref name="ref7" />.
 +
''GAS5'' is a snoRNA host and a functional RNA. Function does not require putative but nonconserved ORF, or the intronic snoRNAs <ref name="ref5" /><ref name="ref6" /><ref name="ref7" />.
  
===Evolution===
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===Regulation===
Please input evolution information here.
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''GAS5'' can be regulated by mTOR, with mTOR (which promotes cellular proliferation) acting to inhibit the function of ''GAS5'' <ref name="ref6" />.
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Expression of ''GAS5'' mRNA is regulated at the posttranscriptional level during growth and at the transcriptional level in
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differentiated cells <ref name="ref2" />.
  
 
===Disease===
 
===Disease===
autoimmune disease, B-cell neoplasms, breast cancer, kidney cancer, lymphoma, prostate cancer, melanoma, systemic lupus erythaematosus
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*Autoimmune disease <ref name="ref6" />
 
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*B-cell neoplasms <ref name="ref6" />
You can also add sub-section(s) at will.
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*Breast cancer <ref name="ref5" />
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*Kidney cancer <ref name="ref6" />
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*Lymphoma <ref name="ref6" />
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*Prostate cancer melanoma <ref name="ref6" />
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*Systemic lupus erythaematosus <ref name="ref6" />
  
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===Expression===
 +
''GAS5'' is widely expressed in adult tissues and over embryonic development <ref name="ref1" />. Transcript undergoes post-transcriptional regulation, highly unstable but stabilised by growth arrest, serum starvation and inhibition of protein synthesis <ref name="ref2" /><ref name="ref4" /><ref name="ref7" />. Associates with ribosomes in the cytoplasm <ref name="ref4" />. Localises to both the nucleus and the cytoplasm <ref name="ref7" />. Down-regulated in breast cancer <ref name="ref5" />. Transcript was classified as unstable with a half-life >4 hr in human Hela cells <ref name="ref8" />.
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===Sequence===
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>gi|60674|ref|NR_002578.3| Homo sapiens growth arrest specific 5 (GAS5), transcript variant 1, long non-coding RNA
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<dnaseq>GTCTTTTCGAGGTAGGAGTCGACTCCTGTGAGGTATGGTGCTGGGTGCAGATGCAGTGTGGCTCTGGATA
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GCACCTTATGGACAGTTGTGTCCCCAAGGAAGGATGAGAATAGCTACTGAAGTCCTAAAGAGCAAGCCTA
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ACTCAAGCCATTGGCACACAGGCATTAGACAGAAAGCTGGAAGTTGAAATGGTGGAGTCCAACTTGCCTG
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GACCAGCTTAATGGTTCTGCTCCTGGTAACGTTTTTATCCATGGATGACTTGCTTGGGTAAGGACATGAA
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GACAGTTCCTGTCATACCTTTTAAAGGTATGGAGAGTCGGCTTGACTACACTGTGTGGAGCAAGTTTTAA
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AGAAGCAAAGGACTCAGAATTCATGATTGAAGAAATGCAGGCAGACCTGTTATCCTAAACTAGGGTTTTT
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AATGACCACAACAAGCAAGCATGCAGCTTACTGCTTGAAAGGGTCTTGCCTCACCCAAGCTAGAGTGCAG
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TGGCCTTTGAAGCTTACTACAGCCTCAAACTTCTGGGCTCAAGTGATCCTCAGCCTCCCAGTGGTCTTTG
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TAGACTGCCTGATGGAGTCTCATGGCACAAGAAGATTAAAACAGTGTCTCCAATTTTAATAAATTTTTGC
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AATCCATCAAAAAAAAAAAAAAAAAA</dnaseq>
 
==Labs working on this lncRNA==
 
==Labs working on this lncRNA==
Please input related labs here.
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*European Molecular Biology Laboratory, Heidelberg, Germany
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*Institute for Science and Technology in Medicine and School of Life Sciences, Huxley Building, Keele University, Keele, United Kingdom
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*King's College London, Department of Haematological Medicine, The Rayne Institute, London, United Kingdom (F.F.)
  
 
==References==
 
==References==
[http://www.lncrnadb.org/GAS5/ Annotation originally sourced from lncRNAdb.]
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<references>
 
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<ref name="ref1"> Schneider C, King RM & Philipson L. Genes Specifically Expressed at Growth Arrest of Mammalian-Cells[J]. Cell. 1988, 54(6):787-793.
{{basic|
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</ref>(1)
tID = NONHSAT007663|
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<ref name="ref2"> 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.
source = NONCODE4.0|
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</ref>(2)
same = ,|
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<ref name="ref3">  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
classification = intergenic|
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</ref>(3)
length = 651 nt|
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<ref name="ref4">  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
location = chr1-:173833039..173837125|
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</ref>(4)
number = 12|
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<ref name="ref5">  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.
exons = 173833039..173833213,173833395..173833442,173833622..173833644,173833813..173833842,173834367..173834420,173834609..173834685,173834995..173835032,173835315..173835344,173835666..173835705,173835899..173835934,173836129..173836181,173837098..173837125|
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</ref>(5)
context = <html><div align="center">
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<ref name="ref6"> 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.
<iframe src="http://lncrna.big.ac.cn/view/?data=species/human&loc=chr1:173833039..173837125&tracklist=0&overview=0&tracks=DNA,RefGene,lncRNA" style=" border-width:0 " width="100%" height="250" scrolling="yes"></iframe>
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</ref>(6)
</div></html>|
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<ref name= "ref7"> 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).
sequence = <dnaseq>TTTCGAGGTAGGAGTCGACTCCTGTGAGGTATGGTGCTGGGTGCGGATGCAGTGTGGCTCTGGATAGCACCTTATGGACAGTTGTGTCCCCAAGGAAGGATGAGAATAGCTACTGAAGTCCTAAAGAGCAAGCCTAACTCAAGCCATTGGCACACAGGCATTAGACAGAAAGCTGGAAGTTGAAATGGTGGAGTCCAACTTGCCTGGACCAGCTTAATGGTTCTGCTCCTGGTAACGTTTTTATCCATGGATGACTTGCTTGGGTAAGGACATGAAGACAGTTCCTGTCATACCTTTTAAAGGTATGGAGAGTCGGCTTGACTACACTGTGTGGAGCAAGTTTTAAAGAAGCAAAGGACTCAGAATTCATGATTGAAGAAATGCAGGCAGACCTGTTATCCTAAACTAGGGTTTTTAATGACCACAACAAGCAAGCATGCAGCTTACTGCTTGAAAGGGTCTTGCCTCACCCAAGCTAGAGTGCAGTGGCCTTTGAAGCTTACTACAGCCTCAAACTTCTGGGCTCAAGTGATCCTCAGCCTCCCAGTGGTCTTTGTAGACTGCCTGATGGAGTCTCATGGCACAAGAAGATTAAAACAGTGTCTCCAATTTTAATAAATTTTTGCAATCCAAAAAAAAAAAAAAAAAAAA</dnaseq>|
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</ref>(7)
}}
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<ref name= "ref8">  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
[[Category:Intergenic]][[Category:NONHSAG003504]][[Category:Transcripts]]
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</ref>(8)
 +
<ref name="ref9"> Zhang X Q , Sun S , Lam K F , et al. A long non-coding RNA signature in glioblastoma multiforme predicts survival[J]. Neurobiology of Disease, 2013, 58:123-131.
 +
</ref>(9)
 +
</references>

Latest revision as of 01:55, 13 August 2019

GAS5, functions as a ceRNA to regulate hZIP1

Annotated Information

Name

Approved symbol: GAS5

Approved name: GAS5: growth arrest specific 5

Alias symbols: SNHG2, NCRNA00030

HGNC ID: HGNC: 16355

LncBook ID: HSALNT0017702

Ensembl ID: ENSG00000234741

RefSeq ID: NR_002578

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]

GAS5 is one of the lncRNAs in a six-lncRNA signature that is independently associated with the prognosis of GBM patients[5].

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 [6]. 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 [7]. GAS5 also appears to repress the action of many steroid hormone receptors, showing some similarities to another lncRNA SRA [7]. GAS5 is a snoRNA host and a functional RNA. Function does not require putative but nonconserved ORF, or the intronic snoRNAs [6][8][7].

Regulation

GAS5 can be regulated by mTOR, with mTOR (which promotes cellular proliferation) acting to inhibit the function of GAS5 [8]. Expression of GAS5 mRNA is regulated at the posttranscriptional level during growth and at the transcriptional level in differentiated cells [2].

Disease

  • Autoimmune disease [8]
  • B-cell neoplasms [8]
  • Breast cancer [6]
  • Kidney cancer [8]
  • Lymphoma [8]
  • Prostate cancer melanoma [8]
  • Systemic lupus erythaematosus [8]

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][7]. Associates with ribosomes in the cytoplasm [4]. Localises to both the nucleus and the cytoplasm [7]. Down-regulated in breast cancer [6]. Transcript was classified as unstable with a half-life >4 hr in human Hela cells [9].

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

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. Zhang X Q , Sun S , Lam K F , et al. A long non-coding RNA signature in glioblastoma multiforme predicts survival[J]. Neurobiology of Disease, 2013, 58:123-131.
  6. 6.0 6.1 6.2 6.3 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.
  7. 7.0 7.1 7.2 7.3 7.4 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).
  8. 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 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.
  9. 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