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

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Science Signaling  02 Feb 2010:
Vol. 3, Issue 107, pp. ra8
DOI: 10.1126/scisignal.2000568

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Noncoding RNA Decoys

Steroid receptors are transcription factors that are activated by ligand binding, which allows these proteins to bind specific sequences called “response elements” in the promoters of target genes to stimulate transcription. Now, Kino et al. find that a noncoding RNA can also interact with steroid receptors and inhibit their binding to the DNA response elements, thereby repressing steroid receptor activity. The authors found that the noncoding RNA growth arrest–specific 5 (Gas5), which accumulates in cells that have been deprived of nutrients or growth factors, bound to the glucocorticoid receptor and competed with DNA glucocorticoid response elements for binding to the receptor, thereby inhibiting glucocorticoid-mediated transcription. This sensitized cells to undergo apoptosis in response to stress by preventing the glucocorticoid-mediated transcription of antiapoptotic genes. Gas5 also interacted with other steroid receptors and inhibited their transcriptional activity, suggesting that decoy RNA response elements may be a common mechanism for regulating transcription factor activity.