title: A critical role for non-coding RNA GAS5 in growth arrest and rapamycin inhibition in human T-lymphocytes.
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.
authors.affiliation: Institute for Science and Technology in Medicine and School of Life Sciences, Huxley Building, Keele University, Keele ST5 5BG, UK. g.t.williams@keele.ac.uk
authors.forename: Gwyn T
authors.initials: GT
authors.lastname: Williams
authors.forename: Mirna
authors.initials: M
authors.lastname: Mourtada-Maarabouni
authors.forename: Farzin
authors.initials: F
authors.lastname: Farzaneh
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000235:genetics*; D006801:Humans; D020537:RNA, Small Nucleolar / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D022661:RNA, Untranslated / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D020537:RNA, Small Nucleolar; D022661:RNA, Untranslated; C109857:growth arrest specific transcript 5; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus