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.
Sci Signal. 2010 Feb 2;3(107):ra8. doi: 10.1126/scisignal.2000568.
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.
营养素的可用性通过影响基因转录来影响细胞生长和存活。糖皮质激素也影响基因转录,并对细胞生长、能量消耗和存活具有多种活性。我们发现,生长停滞特异性 5(Gas5)非编码 RNA 在因缺乏营养或生长因子而生长停滞的细胞中含量丰富,通过抑制糖皮质激素介导的几种反应基因的诱导,包括编码细胞凋亡抑制剂 2 的基因,使细胞对细胞凋亡敏感。Gas5 作为诱饵糖皮质激素反应元件(GRE)与糖皮质激素受体(GR)的 DNA 结合域结合,从而与 GR 竞争 DNA GRE 的结合。我们的结论是,Gas5 是 GR 的“核糖抑制剂”,通过调节 GR 的转录活性,在饥饿期间影响细胞存活和代谢活动。