GAS5 Gene

Tetsuro Hirose, Biomedicinal Information Research Center, Tokyo, Japan

Published online: January 2011

DOI: 10.1002/9780470015902.a0005019.pub2

GAS5 (growth arrest-specific 5) 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. It is ubiquitously expressed, but the spliced GAS5 transcript is rapidly degraded in proliferating cells. Growth-dependent translation mediated by the 5¢ TOP sequence present at its 5¢-terminus determines the level of the GAS5 spliced transcript by a mechanism of translation-linked RNA degradation. The spliced GAS5 transcript plays a critical role in arresting cell growth and inducing apoptosis. The decreased expression of GAS5 in breast cancer suggests that GAS5 acts as a tumour suppressor. The spliced GAS5 transcript suppresses steroid-responsive transcription by direct association of the several steroid receptors and acts as a molecular decoy.

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 to induce apoptosis.
  • GAS5 binds to steroid hormone receptors through its 3¢-terminal stem-loop structure to suppress steroid-responsive transcription.

Keywords: GAS5 gene; small nucleolar RNA; nonprotein-coding gene; 5¢ TOP; nonsense-mediated RNA decay; molecular decoy

Figure 1. GAS5 is a multi-snoRNA host gene in the human and mouse. White boxes represent the 12 exons of human and mouse GAS5; shaded boxes represent the snoRNA sequences present within 10 (in the human) or 9 (in the 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) and box D (terminal CUGA), and rRNA sequences targeted for 2¢ O-methylation (2¢-O-Me) 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 nonsense-mediated decay. 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 (mRNP, messenger ribonucleoprotein).
Figure 4. The spliced GAS5 is a suppressor of steroid hormone receptors. GAS5 binds 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 on GAS5 and GR-responsive promoter.
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 References
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    Filipowicz W and Pogaci V (2002) Biogenesis of small nucleolar ribonucleoproteins. Current Opinion in Cellular Biology 14: 319–327.
    Ganot P, Bortolin ML and Kiss T (1997) Site-specific pseudouridine formation in pre-ribosomal RNA is guided by small nucleolar RNAs. Cell 89: 799–809.
    Hirose T and Steitz JA (2001) Position within the host intron is critical for efficient processing of box C/D snoRNAs in mammalian cells. Proceedings of the National Academy of Sciences of the USA 98: 12914–12919.
    Jeffries HBJ, Fumagalli S, Dennis PB et al. (1997) Rapamycin suppresses 5¢TOP mRNA translation through inhibition of p70S6K. EMBO Journal 12: 3693–3704.
    Lejeune F and Maquat LE (2005) Mechanistic links between nonsense-mediated mRNA decay and pre-mRNA splicing in mammalian cells. Current Opinion in Cellular Biology 17: 309–315.
    Smith CM and Steitz JA (1997) Sno storm in the nucleolus: new roles for myriad small RNPs. Cell 89: 669–672.
    Wilusz JE, Sunwoo H and Spector DL (2009) Long noncoding RNAs: functional surprises from the RNA world. Genes & Development 23: 1494–1504.
 Web Links
    ePath Growth arrest-specific 5 (GAS5); Locus ID: 60674. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=60674
    ePath RNA, U17D small nucleolar (RNU17D); Locus ID: 8420. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=8420
    ePath RNA, U19 small nucleolar (RNU19); Locus ID: 26821. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=26821
    ePath RNA, U22 small nucleolar (RNU22); Locus ID: 9304. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=9304
    ePath RNA, U17D small nucleolar (RNU17D); MIM number: 603238. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?603238
    ePath RNA, U22 small nucleolar (RNU22); MIM number: 603222. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?603222

Related Sub-Topics:

Cell Biology of Cancer | Cell Death and Cellular Senescence | Cancer Genetics | RNA Structure and Function | Noncoding RNA | Mechanisms of Cell Death, Senescence and Metabolism
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Article Title: GAS5 Gene
 
How to Cite close
Hirose, Tetsuro(Jan 2011) GAS5 Gene. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005019.pub2]