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GAS5 (growth arrest-specific 5 (non-protein coding))

Written2009-10Mirna Mourtada-Maarabouni
Institute for Science, Technology in Medicine, Huxley Building, Keele University, Keele, Staffordshire ST5 5BG, UK

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)SNHG2
NCRNA00030
HGNC (Hugo) GAS5
LocusID (NCBI) 60674
Atlas_Id 50217
Location 1q25.1  [Link to chromosome band 1q25]
Location_base_pair Starts at 173833039 and ends at 173837125 bp from pter ( according to hg19-Feb_2009)  [Mapping GAS5.png]
Fusion genes
(updated 2016)
GAS5 (1q25.1) / BCL6 (3q27.3)GAS5 (1q25.1) / DHCR24 (1p32.3)GAS5 (1q25.1) / DPH2 (1p34.1)
GAS5 (1q25.1) / ENG (9q34.11)GAS5 (1q25.1) / HADHA (2p23.3)GAS5 (1q25.1) / HNRNPUL1 (19q13.2)
GAS5 (1q25.1) / LILRA6 (19q13.42)GAS5 (1q25.1) / ORMDL1 (2q32.2)GAS5 (1q25.1) / PABPC1L (20q13.12)
GAS5 (1q25.1) / RAB29 (1q32.1)GAS5 (1q25.1) / RPL36A-HNRNPH2 (Xq22.1)GAS5 (1q25.1) / RPL7A (9q34.2)
GAS5 (1q25.1) / SCGN (6p22.2)GAS5 (1q25.1) / TNFRSF1A (12p13.31)PER1 (17p13.1) / GAS5 (1q25.1)
Note GAS5 is also designed as small nucleolar RNA host gene (non-protein coding) 2 and non-protein coding RNA 30.
1q25 locus displays abnormalities in a number of cancers, melanoma, prostate, breast and several types of leukaemia and lymphoma. The GAS5 gene was isolated from NIH 3T3 cells using subtraction hybridisation, in a screen intended to isolate potential tumor suppressor genes. The functions of GAS5 is not well known as yet, however, emerging evidence implicates this gene in apoptosis, autoimmune disease, leukemias and lymphomas, and other cancers.

DNA/RNA

 
  Representation of five of GAS5 splice variants. Boxes numbered 2 to12 represent exons. U79, U80, U47, U81 and U74 represent the box C/D small nucleolar RNAs (snoRNAs). Horizontal lines represent the intronic sequences. Exons, introns and snoRNAs are not drawn to scale (IMAGE clone 6194071, 1249 bp; IMAGE clone 2598129, 1270 bp; IMAGE clone 3585621, 1396 bp; Gas5 3A, 1802 bp; IMAGE clone 5739605, 1802 bp; IMAGE clone 2761825, 1802 bp).
Description The gene spans about 4.98 Kb. Orientation minus strand. Number of exons: 12. GenBank: AF141346.1. GAS5 gene hosts multiple small nucleolar RNA (snoRNA) host gene similar to UHG (U22 host gene) which encode, within the 11 introns of the human GAS5 gene, ten box C/D snoRNAs predicted to play a role in the 2'-O-methylation of rRNA. Its 5' end sequence contains an oligopyrimidine tract characteristic of the 5'-TOP class of genes.
Transcription The length of GAS5 transcript is 651bp (NR_002578 in GenBank). The 5' end sequence of the GAS5 transcript contains an oligopyrimidine tract characteristic of the 5'-TOP class of genes. GAS5 transcripts display several patterns of alternate splicing. The initial GAS5 transcript is subject to complex post-transcriptional processing resulting in several splice variants. However its putative open reading frame is small and poorly conserved during even relatively short periods of evolution, as demonstrated by a number of disruptions caused by frameshift mutations in several mouse strains, and by an interruption by a stop codon after the first 13 amino acids in rat GAS5. The diagram above shows some of GAS5 splice variants which are reported to affect cell fate in different ways.

Protein

Note GAS5 exons do not encode a polypeptide product.

Mutations

Note Chromosomal rearrangements involving GAS5 have been identified in a human B-cell lymphoma where GAS5 gene becomes fused to the BCL6 gene. GAS5 is also involved in a chromosomal rearrangement with Notch1 in radiation-induced murine thymic lymphoma.

Implicated in

Note
  
Entity Regulation of cell growth
Note The GAS5 gene was isolated from NIH 3T3 cells using subtraction hybridisation, in a screen intended to isolate potential tumor suppressor genes. GAS5 is reported to be ubiquitously expressed during mouse development and adult life, and also to be expressed only at low levels in actively growing Friend leukemia and NIH 3T3 cells, with substantially increased abundance in cells grown to saturation density. The RNA levels of GAS5 appear to be regulated primarily through changes in its rate of degradation rather than through changes in its transcription rate. GAS5 RNA abundance was also found to be increased by amino acid deprivation. Studies also have shown that GAS5 is necessary and sufficient for growth arrest in both untransformed and leukaemic lymphocytes.
  
  
Entity Systemic lupus erythematosus
Note The GAS5 gene is located in the disease susceptibility locus in mouse BXSB strain, which develops glomerulonephritis associated with systemic lupus erythematosus (SLE). Subsequent studies involving genetic analysis of a mouse model of SLE have indicated that GAS5 may well be involved in its pathology. Besides, the human chromosomal locus 1q25 at which the GAS5 gene is encoded has been associated with SLE in genetic studies in humans.
  
  
Entity Apoptosis/cell cycle regulation
Note A fragment of GAS5 cDNA has been isolated from a retroviral cDNA expression library by using an unbiased functional screen for genes that control apoptosis in lymphocytes. Further studies have shown that GAS5 plays an essential role in normal growth arrest in both T-cell lines and non-transformed lymphocytes. Overexpression of GAS5 causes both an enhancement in apoptosis and a decrease in the rate of progression through the cell cycle in leukeamic T cell lines and primary lymphocytes. Consistent with this, downregulation of endogenous GAS5 inhibits apoptosis and maintains a more rapid cell cycle, indicating that GAS5 expression is both essential and sufficient for normal growth arrest in T-cell lines as well as human peripheral blood T-cells. Overexpression of certain GAS5 transcripts is reported to induce growth arrest and apoptosis in several mammalian cell lines.
  
  
Entity Oncogenesis
Note GAS5 is encoded at 1q25, a locus displaying abnormalities in a number of cancers, e.g. melanoma, prostate, breast, and several types of leukaemia and lymphoma. Gene expression analysis has shown that GAS5 is up-regulated 3.3-fold (the greatest up-regulation for any gene in the whole-genome array) by oncogenic kinases associated with myeloproliferative disorders. Chromosomal rearrangements involving GAS5 have also been identified in a human B-cell lymphoma. GAS5 expression levels are reported to regulate both the induction of apoptosis and cell cycle arrest in T-cell lines and non-transformed lymphocytes, suggesting that it may be very significant in the development of leukaemia and lymphoma. Overexpression of certain GAS5 transcripts is reported to induce growth arrest and apoptosis in several human cell lines, including human breast cancer cell lines. GAS5 expression is significantly downregulated in breast cancer tissue compared with those found in untransformed breast epithelial tissue from the same patients, a clear reduction of more than 65% was observed in this study, suggesting that the reduction in GAS5 expression is an early event in oncogenesis.
  

Bibliography

Regulation and expression of a growth arrest-specific gene (gas5) during growth, differentiation, and development.
Coccia EM, Cicala C, Charlesworth A, Ciccarelli C, Rossi GB, Philipson L, Sorrentino V.
Mol Cell Biol. 1992 Aug;12(8):3514-21.
PMID 1630459
 
Effects of nutrient deprivation and differentiation on the expression of growth-arrest genes (gas and gadd) in F9 embryonal carcinoma cells.
Fleming JV, Hay SM, Harries DN, Rees WD.
Biochem J. 1998 Feb 15;330(Pt 1):573-9.
PMID 9461558
 
Amino acid deficiency up-regulates specific mRNAs in murine embryonic cells.
Fontanier-Razzaq N, Harries DN, Hay SM, Rees WD.
J Nutr. 2002 Aug;132(8):2137-42.
PMID 12163652
 
Overlapping BXSB congenic intervals, in combination with microarray gene expression, reveal novel lupus candidate genes.
Haywood ME, Rose SJ, Horswell S, Lees MJ, Fu G, Walport MJ, Morley BJ.
Genes Immun. 2006 Apr;7(3):250-63.
PMID 16541099
 
A major susceptibility locus for systemic lupus erythemathosus maps to chromosome 1q31.
Johanneson B, Lima G, von Salome J, Alarcon-Segovia D, Alarcon-Riquelme ME; Collaborative Group on the Genetics of SLE, The BIOMED II Collaboration on the Genetics of SLE and Sjogrens syndrome.
Am J Hum Genet. 2002 Nov;71(5):1060-71. Epub 2002 Oct 8.
PMID 12373647
 
Oncogenic kinases of myeloproliferative disorders induce both protein synthesis and G1 activators.
Lelievre H, Cervera N, Finetti P, Delhommeau F, Vainchenker W, Bertucci F, Birnbaum D.
Leukemia. 2006 Oct;20(10):1885-8. Epub 2006 Aug 10.
PMID 16900207
 
GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer.
Mourtada-Maarabouni M, Pickard MR, Hedge VL, Farzaneh F, Williams GT.
Oncogene. 2009 Jan 15;28(2):195-208. Epub 2008 Oct 6.
PMID 18836484
 
The gas5 gene is disrupted by a frameshift mutation within its longest open reading frame in several inbred mouse strains and maps to murine chromosome 1.
Muller AJ, Chatterjee S, Teresky A, Levine AJ.
Mamm Genome. 1998 Sep;9(9):773-4.
PMID 9716666
 
The GAS5 (growth arrest-specific transcript 5) gene fuses to BCL6 as a result of t(1;3)(q25;q27) in a patient with B-cell lymphoma.
Nakamura Y, Takahashi N, Kakegawa E, Yoshida K, Ito Y, Kayano H, Niitsu N, Jinnai I, Bessho M.
Cancer Genet Cytogenet. 2008 Apr 15;182(2):144-9.
PMID 18406879
 
The gas 5 gene shows four alternative splicing patterns without coding for a protein.
Raho G, Barone V, Rossi D, Philipson L, Sorrentino V.
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PMID 11054530
 
Genes specifically expressed at growth arrest of mammalian cells.
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Characterization of chromosome 1 abnormalities in malignant melanomas.
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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.
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High-resolution genomic profiling reveals association of chromosomal aberrations on 1q and 16p with histologic and genetic subgroups of invasive breast cancer.
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Radiation-induced deletions in the 5' end region of Notch1 lead to the formation of truncated proteins and are involved in the development of mouse thymic lymphomas.
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Isolation of genes controlling apoptosis through their effects on cell survival.
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Citation

This paper should be referenced as such :
Mourtada-Maarabouni, M
GAS5 (growth arrest-specific 5 (non-protein coding))
Atlas Genet Cytogenet Oncol Haematol. 2010;14(8):758-760.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/GAS5ID50217ch1q25.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(1;3)(q25;q27) GAS5/BCL6


External links

Nomenclature
HGNC (Hugo)GAS5   16355
Cards
AtlasGAS5ID50217ch1q25
Entrez_Gene (NCBI)GAS5  60674  growth arrest specific 5 (non-protein coding)
AliasesNCRNA00030; SNHG2
GeneCards (Weizmann)GAS5
Ensembl hg19 (Hinxton)ENSG00000234741 [Gene_View]  chr1:173833039-173837125 [Contig_View]  GAS5 [Vega]
Ensembl hg38 (Hinxton)ENSG00000234741 [Gene_View]  chr1:173833039-173837125 [Contig_View]  GAS5 [Vega]
ICGC DataPortalENSG00000234741
TCGA cBioPortalGAS5
AceView (NCBI)GAS5
Genatlas (Paris)GAS5
WikiGenes60674
SOURCE (Princeton)GAS5
Genetics Home Reference (NIH)GAS5
Genomic and cartography
GoldenPath hg19 (UCSC)GAS5  -     chr1:173833039-173837125 -  1q25.1   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)GAS5  -     1q25.1   [Description]    (hg38-Dec_2013)
EnsemblGAS5 - 1q25.1 [CytoView hg19]  GAS5 - 1q25.1 [CytoView hg38]
Mapping of homologs : NCBIGAS5 [Mapview hg19]  GAS5 [Mapview hg38]
OMIM608280   
Gene and transcription
Genbank (Entrez)AK025846 AL110141 BC038733 BC070486 HG975395
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)NC_000001 NC_018912 NT_004487 NW_004929293
Consensus coding sequences : CCDS (NCBI)GAS5
Cluster EST : UnigeneHs.736055 [ NCBI ]
CGAP (NCI)Hs.736055
Alternative Splicing GalleryENSG00000234741
Gene ExpressionGAS5 [ NCBI-GEO ]   GAS5 [ EBI - ARRAY_EXPRESS ]   GAS5 [ SEEK ]   GAS5 [ MEM ]
Gene Expression Viewer (FireBrowse)GAS5 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)60674
GTEX Portal (Tissue expression)GAS5
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)GAS5
DMDM Disease mutations60674
Blocks (Seattle)GAS5
Human Protein AtlasENSG00000234741
Protein Interaction databases
FunCoupENSG00000234741
BioGRIDGAS5
STRING (EMBL)GAS5
ZODIACGAS5
Ontologies - Pathways
Huge Navigator GAS5 [HugePedia]
snp3D : Map Gene to Disease60674
BioCentury BCIQGAS5
ClinGenGAS5
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD60674
Chemical/Pharm GKB GenePA28581
Clinical trialGAS5
Miscellaneous
canSAR (ICR)GAS5 (select the gene name)
Probes
Litterature
PubMed33 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineGAS5
EVEXGAS5
GoPubMedGAS5
iHOPGAS5
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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