Noncoding RNA gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor.
The availability of nutrients influences cellular growth and survival by affecting gene transcription. Glucocorticoids also influence gene transcription and have diverse activities on cell growth, energy expenditure, and survival. We found that the growth arrest-specific 5 (Gas5) noncoding RNA, which is abundant in cells whose growth has been arrested because of lack of nutrients or growth factors, sensitized cells to apoptosis by suppressing glucocorticoid-mediated induction of several responsive genes, including the one encoding cellular inhibitor of apoptosis 2. Gas5 bound to the DNA-binding domain of the glucocorticoid receptor (GR) by acting as a decoy glucocorticoid response element (GRE), thus competing with DNA GREs for binding to the GR. We conclude that Gas5 is a "riborepressor" of the GR, influencing cell survival and metabolic activities during starvation by modulating the transcriptional activity of the GR.
Kino
Tomoshige
T
Unit on Molecular Hormone Action, Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1109, USA. kinot@mail.nih.gov
Hurt
Darrell E
DE
Ichijo
Takamasa
T
Nader
Nancy
N
Chrousos
George P
GP
D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D001667:Binding, Competitive / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells; D009690:Nucleic Acid Conformation; D020537:RNA, Small Nucleolar / Q000235:genetics* / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases
D003470:Culture Media; D005938:Glucocorticoids; D051034:Inhibitor of Apoptosis Proteins; D020537:RNA, Small Nucleolar; D022661:RNA, Untranslated; D011965:Receptors, Glucocorticoid; C109857:growth arrest specific transcript 5; D003907:Dexamethasone; D004247:DNA; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases