Janowski Bethany A, Corey David R
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75205, USA.
Mol Endocrinol. 2010 Dec;24(12):2243-52. doi: 10.1210/me.2010-0067. Epub 2010 Jun 30.
It has long been appreciated that gene expression is regulated by protein complexes at promoters. More recently, research has demonstrated that small duplex RNAs such as micro-RNAs and short interfering RNAs complementary to mRNA provide another layer of regulation. Evidence now supports the existence of regulatory pathways that use small duplex RNAs to control transcription. Synthetic RNAs complementary to gene promoters [antigene RNAs (agRNAs)] can either activate or inhibit gene expression. Activity of agRNAs is mediated by argonaute, a protein required for RNA interference. Unlike protein transcription factors, agRNAs do not bind to chromosomal DNA but recognize noncoding transcripts that overlap gene promoters or 3'-gene termini. This review describes recent studies with agRNAs and focuses on the robust and potent agRNA-mediated regulation of progesterone receptor. The ability of small RNAs to alter transcription provides a new layer of potential regulation for gene expression.
长期以来,人们一直认识到基因表达受启动子处的蛋白质复合物调控。最近,研究表明,诸如微小RNA和与mRNA互补的短干扰RNA之类的小双链RNA提供了另一层调控。现在有证据支持存在利用小双链RNA来控制转录的调控途径。与基因启动子互补的合成RNA [反基因RNA(agRNA)]可以激活或抑制基因表达。agRNA的活性由AGO介导,AGO是RNA干扰所需的一种蛋白质。与蛋白质转录因子不同,agRNA不与染色体DNA结合,而是识别与基因启动子或3'-基因末端重叠的非编码转录本。本综述描述了最近关于agRNA的研究,并重点关注了agRNA介导的对孕激素受体的强大调控作用。小RNA改变转录的能力为基因表达提供了新的潜在调控层面。