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Gene Section
Mini Review
GAS5 (growth arrest-specific 5 (non-protein
coding))
Mirna Mourtada-Maarabouni
Institute for Science and Technology in Medicine, Huxley Building, Keele University, Keele, Staffordshire
ST5 5BG, UK (MMM)
Published in Atlas Database: October 2009
Online updated version : http://AtlasGeneticsOncology.org/Genes/GAS5ID50217ch1q25.html
DOI: 10.4267/2042/44823
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology
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.
Identity
Other names: NCRNA00030; SNHG2
HGNC (Hugo): GAS5
Location: 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
DNA/RNA
Description
The gene spans about 4.98 kb. Orientation minus
strand. Number of exons: 12. GenBank: AF141346.1.
GAS5 gene hosts multiple small
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).
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(8)
758
GAS5 (growth arrest-specific 5 (non-protein coding))
Mourtada-Maarabouni M
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.
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.
Transcription
The length of GAS5 transcript is 651 bp (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 posttranscriptional 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.
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.
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.
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 upregulation 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
Implicated in
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.
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(8)
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GAS5 (growth arrest-specific 5 (non-protein coding))
Mourtada-Maarabouni M
Tsuji H, Ishii-Ohba H, Ukai H, Katsube T, Ogiu T. Radiationinduced 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. Carcinogenesis.
2003 Jul;24(7):1257-68
observed in this study, suggesting that the reduction in
GAS5 expression is an early event in oncogenesis.
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This article should be referenced as such:
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(8)
Mourtada-Maarabouni M. GAS5 (growth arrest-specific 5 (nonprotein coding)). Atlas Genet Cytogenet Oncol Haematol.
2010; 14(8):758-760.
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