Department of Microbiology, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Sci Signal. 2010 Feb 9;3(108):pe5. doi: 10.1126/scisignal.3108pe5.
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.
糖皮质激素受体 (GR) 是一种典型的 DNA 结合转录因子,早在 20 多年前就被描述为第一个被鉴定与称为“反应元件”的基因增强子区域结合的蛋白质之一。自那时以来,大量的工作揭示了 GR 的转录调控几乎在其活性的每一个步骤都受到控制:配体结合、核易位、转录共激活因子结合和 DNA 结合。就在 GR 调节的主要模式似乎已经被了解的时候,一项新的研究提供了另一种机制,即在细胞生长停滞的情况下控制 GR 转录活性。在这种情况下,GR 活性被生长停滞特异性转录物 5 基因的小非编码 RNA (ncRNA) 抑制,该 ncRNA 折叠成一个可溶性糖皮质激素反应元件样序列,并作为 GR DNA 结合的诱饵。这种由核酸分子模拟引起的出乎意料的调控模式可能不仅限于 GR,应该会激发人们对寻找其他调节转录因子与 DNA 结合的 ncRNA 的兴趣。