NONHSAT007663

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Annotated Information

Name

GAS5

Characteristics

Growth arrest-specific transcript (Schneider (1988)), multiple splice isoforms (Coccia (1992)) of ~250, ~450, ~600nuc and longer (Mourtada-Maarabouni (2008)), encodes 9 (10 in humans) snoRNAs in its introns (Smith (1998)).

Function

Necessary and sufficient for growth arrest in human peripheral blood T-cells. Functions by controlling apoptosis and the cell cycle in lymphocytes (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 (Mourtada-Maarabouni (2009)). Gas5 can be regulated by mTOR, with mTOR (which promotes cellular proliferation) acting to inhibit the function of Gas5 (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 (Kino (2010)). Gas5 also appears to repress the action of many steroid hormone receptors, showing some similarities to another lncRNA SRA (Kino (2010)). Gas5 is a snoRNA host and a functional RNA. Function does not require putative but nonconserved ORF, or the intronic snoRNAs (Mourtada-Maarabouni (2008), Mourtada-Maarabouni (2009), Kino (2010)).

Expression

Widely expressed in adult tissues and over embryonic development (Coccia (1992)). Transcript undergoes post-transcriptional regulation, highly unstable but stabilised by growth arrest, serum starvation and inhibition of protein synthesis (Coccia (1992), Smith (1998), Kino (2010)). Associates with ribosomes in the cytoplasm (Smith (1998)). Localises to both the nucleus and the cytoplasm (Kino (2010))]. Down-regulated in breast cancer (Mourtada-Maarabouni (2009)). Transcript was classified as unstable with a half-life >4 hr in human Hela cells (Tani (2012)). Similar half-lives were identified in human B cells and mouse 3T3 fibroblasts (Friedel (2009), Clark (2012)).

Conservation

Gas5 in mouse and human do not show high sequence identity (Tanaka-Fujita (2007)) although the GRE mimmic region is conserved (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 (Shao (2009)).

Misc

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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Regulation

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Allelic Information and Variation

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Evolution

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Disease

autoimmune disease, B-cell neoplasms, breast cancer, kidney cancer, lymphoma, prostate cancer, melanoma, systemic lupus erythaematosus

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Labs working on this lncRNA

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References

Annotation originally sourced from lncRNAdb.

Basic Information

Transcript ID	NONHSAT007663
Source	NONCODE4.0
Same with	,
Classification	intergenic
Length	651 nt
Genomic location	chr1-:173833039..173837125
Exon number	12
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
Genome context
Sequence	000001 TTTCGAGGTA GGAGTCGACT CCTGTGAGGT ATGGTGCTGG GTGCGGATGC AGTGTGGCTC TGGATAGCAC CTTATGGACA 000080 000081 GTTGTGTCCC CAAGGAAGGA TGAGAATAGC TACTGAAGTC CTAAAGAGCA AGCCTAACTC AAGCCATTGG CACACAGGCA 000160 000161 TTAGACAGAA AGCTGGAAGT TGAAATGGTG GAGTCCAACT TGCCTGGACC AGCTTAATGG TTCTGCTCCT GGTAACGTTT 000240 000241 TTATCCATGG ATGACTTGCT TGGGTAAGGA CATGAAGACA GTTCCTGTCA TACCTTTTAA AGGTATGGAG AGTCGGCTTG 000320 000321 ACTACACTGT GTGGAGCAAG TTTTAAAGAA GCAAAGGACT CAGAATTCAT GATTGAAGAA ATGCAGGCAG ACCTGTTATC 000400 000401 CTAAACTAGG GTTTTTAATG ACCACAACAA GCAAGCATGC AGCTTACTGC TTGAAAGGGT CTTGCCTCAC CCAAGCTAGA 000480 000481 GTGCAGTGGC CTTTGAAGCT TACTACAGCC TCAAACTTCT GGGCTCAAGT GATCCTCAGC CTCCCAGTGG TCTTTGTAGA 000560 000561 CTGCCTGATG GAGTCTCATG GCACAAGAAG ATTAAAACAG TGTCTCCAAT TTTAATAAAT TTTTGCAATC CAAAAAAAAA 000640 000641 AAAAAAAAAA A

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