Glucocorticoid Receptor DNA Binding Decoy Is a Gas

The glucocorticoid receptor (GR) is a paradigmatic DNA binding transcription factor and was described over 20 years ago as one of the first proteins identified to bind the enhancer region of genes called response elements. Since that time, an immense amount of work has revealed that GR transcriptional regulation is controlled at virtually every step of its activity: ligand binding, nuclear translocation, transcriptional cofactor binding, and DNA binding. Just when the major modes of GR regulation appear known, a new study provides yet another mechanism whereby GR transcriptional activity is controlled under conditions of cell growth arrest. In this case, GR activity is repressed by a small noncoding RNA (ncRNA) from the growth arrest-specific transcript 5 gene that folds into a soluble glucocorticoid response element-like sequence and serves as a decoy for GR DNA binding. This unexpected mode of regulation by nucleic acid molecular mimicry is probably not confined to GR and should spark interest in the hunt for other ncRNAs that regulate transcription factor binding to DNA.