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Sci. Signal., 2 February 2010
Vol. 3, Issue 107, p. ra8
[DOI: 10.1126/scisignal.2000568]

RESEARCH ARTICLES

Noncoding RNA Gas5 Is a Growth Arrest– and Starvation-Associated Repressor of the Glucocorticoid Receptor

Tomoshige Kino1*, Darrell E. Hurt2, Takamasa Ichijo1, Nancy Nader1, and George P. Chrousos3

1 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, Building 10, Clinical Research Center, Rm. 1-3140, 10 Center Drive MSC 1109, Bethesda, MD 20892–1109, USA.
2 Bioinformatics and Scientific IT Program, Office of Technology Information Systems, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892–1109, USA.
3 First Department of Pediatrics, Athens University Medical School, Athens 11527, Greece.

Abstract: 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.

* To whom correspondence should be addressed. E-mail: kinot{at}mail.nih.gov

Citation: T. Kino, D. E. Hurt, T. Ichijo, N. Nader, G. P. Chrousos, Noncoding RNA Gas5 Is a Growth Arrest– and Starvation-Associated Repressor of the Glucocorticoid Receptor. Sci. Signal. 3, ra8 (2010).

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