A critical role for non-coding RNA GAS5 in growth arrest and rapamycin inhibition in human T-lymphocytes

Biochem Soc Trans. 2011 Apr;39(2):482-6. doi: 10.1042/BST0390482.

Abstract

Non-coding RNA GAS5 (growth arrest-specific transcript 5) is a 5'-TOP (5'-terminal oligopyrimidine tract) RNA, whose translation, and consequently also stability, is controlled by the mTOR (mammalian target of rapamycin) pathway. GAS5 was identified by functional expression cloning and is necessary and sufficient for normal growth arrest in both leukaemic and untransformed human T-lymphocytes. GAS5 is also required for the inhibitory effects of rapamycin and its analogues on T-cells. The striking functional effects of GAS5 may be mediated through the snoRNAs (small nucleolar RNAs) encoded in its introns and/or through the unusual folding of the mRNA itself, which sequesters, and therefore inhibits, the glucocorticoid receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Growth Processes / genetics*
  • Humans
  • RNA, Small Nucleolar / genetics
  • RNA, Small Nucleolar / metabolism
  • RNA, Small Nucleolar / physiology*
  • RNA, Untranslated / physiology*
  • Sirolimus / pharmacology*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / physiology
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*

Substances

  • RNA, Small Nucleolar
  • RNA, Untranslated
  • growth arrest specific transcript 5
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus