GAS5 Gene

Abstract

Growth arrest‐specific 5 (GAS5) is a nonprotein‐coding small nucleolar ribonucleic acid (snoRNA) host gene. Ten box C/D snoRNAs are encoded within the 11 introns of the human GAS5 gene, whereas the spliced exons have little protein‐coding potential. GAS5 has been classified as a member of the 5′ oligopyrimidine tract (5′ TOP) gene family. Growth‐dependent translation mediated by the 5′ TOP sequence determines the level of the GAS5 spliced transcript (GAS5 long noncoding RNA (lncRNA)) by a mechanism of translation‐linked RNA degradation. GAS5 lncRNA plays a critical role in arresting cell growth and inducing apoptosis. The decreased expression of GAS5 in multiple cancers suggests that GAS5 acts as a tumour suppressor. GAS5 lncRNA controls the gene expression of critical cell cycle and apoptosis regulators. GAS5 lncRNA suppresses steroid‐responsive transcription by direct association with several steroid receptors and acts as a molecular decoy. GAS5 lncRNA also sequestrates a specific functional microRNA.

Key Concepts

  • GAS5 is a nonprotein‐coding small nucleolar RNA host gene.
  • A translation‐linked mRNA decay pathway controls growth arrest‐specific accumulation of GAS5 by way of its 5′‐terminal oligopyrimidine tract (5′ TOP).
  • GAS5 functions to arrest cell growth and induce apoptosis.
  • GAS5 controls expression of genes for critical regulators of the cell cycle and apoptosis.
  • GAS5 binds to steroid hormone receptors through its 3′‐terminal stem‐loop structure to suppress steroid‐responsive transcription.
  • GAS5 sequestrates a specific functional microRNA.

Keywords: GAS5 gene; small nucleolar RNA; nonprotein‐coding gene; 5′ TOP; nonsense‐mediated RNA decay; long noncoding RNA; molecular decoy

Figure 1. GAS5 is a multi‐snoRNA host gene in human and mouse. White boxes represent the 12 exons of human and mouse GAS5; shaded boxes represent the snoRNA sequences present within 10 (in human) or 9 (in mouse) of the introns. The alternative splicing events observed in both human and mouse are indicated. The maps are not to scale.
Figure 2. Box C/D snoRNAs direct site‐specific 2′ O‐methylation of rRNA. Box C (RUGAUGA, where R stands for purine), box D′ (internal CUGA), box C′ (UGAUGA), box D (terminal CUGA) and rRNA sequences targeted for 2′ O‐methylation (2′ OMe) are shown.
Figure 3. Model explaining why GAS5 is a growth arrest‐specific transcript. In growing cells, spliced GAS5 RNA is translated and degraded by NMD. If translation is inhibited, the levels of the GAS5 transcript increase. Likewise, when cell growth is arrested, GAS5 RNA shifts from monosomes into submonosomal particles, where it accumulates and does not undergo translation.
Figure 4. GAS5 lncRNA is a suppressor of steroid hormone receptors. GAS5 binds to several steroid hormone receptors (GR is represented in this figure) through its 3′‐terminal stem loop. The sequestration of GR by GAS5 leads to transcriptional suppression of various GR‐responsive genes. Grey boxes represent the GR‐binding site in GAS5 and the GR‐responsive promoter.
Figure 5. GAS5 lncRNA acts as a molecular sponge of microRNA. GAS5 lncRNA sequestrates functional miR‐21 through interaction with the miR‐21‐binding site in GAS5 exon 4. The binding of miR‐21 results in downregulation of GAS5 lncRNA.
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Further Reading

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Wilusz JE, Sunwoo H and Spector DL (2009) Long noncoding RNAs: functional surprises from the RNA world. Genes & Development 23: 1494–1504.

Web Link

Growth arrest‐specific 5 (GAS5); Locus ID: 60674. LocusLink: http://www.ncbi.nlm.nih.gov/gene/60674

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How to Cite close
Aly, Mahmoud Khamis, and Hirose, Tetsuro(Nov 2016) GAS5 Gene. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005019.pub3]