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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).
Unliganded progesterone receptor-mediated targeting of an RNA-containing repressive complex silences a subset of hormone-inducible genes.
G. P. Vicent, A. S. Nacht, R. Zaurin, J. Font-Mateu, D. Soronellas, F. Le Dily, D. Reyes, and M. Beato (2013)
Genes & Dev.
27, 1179-1197
|Abstract »|Full Text »|PDF »
Non-coding RNAs in homeostasis, disease and stress responses: an evolutionary perspective.
P. P. Amaral, M. E. Dinger, and J. S. Mattick (2013)
Briefings in Functional Genomics
12, 254-278
|Abstract »|Full Text »|PDF »
Long Noncoding RNAs in Cardiac Development and Pathophysiology.
N. Schonrock, R. P. Harvey, and J. S. Mattick (2012)
Circ. Res.
111, 1349-1362
|Abstract »|Full Text »|PDF »
The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression.
T. Derrien, R. Johnson, G. Bussotti, A. Tanzer, S. Djebali, H. Tilgner, G. Guernec, D. Martin, A. Merkel, D. G. Knowles, et al. (2012)
Genome Res.
22, 1775-1789
|Abstract »|Full Text »|PDF »
Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs.
V. A. Moran, R. J. Perera, and A. M. Khalil (2012)
Nucleic Acids Res.
40, 6391-6400
|Abstract »|Full Text »|PDF »
ZNF764 Haploinsufficiency May Explain Partial Glucocorticoid, Androgen, and Thyroid Hormone Resistance Associated with 16p11.2 Microdeletion.
T. Kino, M. G. Pavlatou, A. G. Moraitis, R. L. Nemery, M. Raygada, and C. A. Stratakis (2012)
J. Clin. Endocrinol. Metab.
97, E1557-E1566
|Abstract »|Full Text »|PDF »
miRcode: a map of putative microRNA target sites in the long non-coding transcriptome.
A. Jeggari, D. S. Marks, and E. Larsson (2012)
Bioinformatics
28, 2062-2063
|Abstract »|Full Text »|PDF »
Genome-wide determination of RNA stability reveals hundreds of short-lived noncoding transcripts in mammals.
H. Tani, R. Mizutani, K. A. Salam, K. Tano, K. Ijiri, A. Wakamatsu, T. Isogai, Y. Suzuki, and N. Akimitsu (2012)
Genome Res.
22, 947-956
|Abstract »|Full Text »|PDF »
SNORD-host RNA Zfas1 is a regulator of mammary development and a potential marker for breast cancer.
M. E. Askarian-Amiri, J. Crawford, J. D. French, C. E. Smart, M. A. Smith, M. B. Clark, K. Ru, T. R. Mercer, E. R. Thompson, S. R. Lakhani, et al. (2011)
RNA
17, 878-891
|Abstract »|Full Text »|PDF »
lncRNAdb: a reference database for long noncoding RNAs.
P. P. Amaral, M. B. Clark, D. K. Gascoigne, M. E. Dinger, and J. S. Mattick (2011)
Nucleic Acids Res.
39, D146-D151
|Abstract »|Full Text »|PDF »
Inhibition of Human T-Cell Proliferation by Mammalian Target of Rapamycin (mTOR) Antagonists Requires Noncoding RNA Growth-Arrest-Specific Transcript 5 (GAS5).
M. Mourtada-Maarabouni, A. M. Hasan, F. Farzaneh, and G. T. Williams (2010)
Mol. Pharmacol.
78, 19-28
|Abstract »|Full Text »|PDF »
Glucocorticoid Receptor DNA Binding Decoy Is a Gas.
