Role of GW182 proteins in miRNA-mediated gene silencing

MicroRNAs是基因组编码的小RNA，在转录后调节基因表达，在包括细胞生长、分裂和分化在内的广泛的重要生物学过程中发挥关键作用。为了发挥其调节功能，miRNAs与Argonaute蛋白(AGOS)结合形成RNA诱导的沉默复合体(MiRISCs)，抑制靶mRNAs的翻译和/或触发其降解。MiRNA生物发生所需的蛋白质(即DROSHA和DICER)以及参与沉默效应步骤的ArgAerte蛋白质都具有很好的特性。此外，在不同生物体中的遗传筛选和生化纯化确定了miRNA表达和功能所需的其他因素。其中一些因子是物种、靶标或miRNA特有的；另一些因子在miRNA介导的基因沉默中发挥普遍作用，并在不同的生物体中保守。在发挥普遍作用的蛋白质中，GW182家族的那些蛋白质已经成为动物细胞中miRNA抑制复合体的关键成分。本项目的目的是了解GW182蛋白在miRNA途径中的确切分子功能。

MicroRNAs are genome-encoded small RNAs that post-transcriptionally regulate gene expression and play critical roles in a wide range of important biological processes including cell growth, division and differentiation. To exert their regulatory function, miRNAs associate with Argonaute proteins (AGOs) to form RNA-induced silencing complexes (miRISCs), which repress translation and/or trigger degradation of target mRNAs. The proteins required for miRNA biogenesis (i.e. Drosha and Dicer) are well characterized, as are the Argonaute proteins involved in the effector step of silencing. In addition, genetic screens and biochemical purifications in diverse organisms identified additional factors required for miRNA expression and function. Some of these factors are species, target or miRNA specific; others play a general role in miRNA-mediated gene silencing and are conserved in diverse organisms. Amongst proteins that play a general role, those in the GW182 family have emerged as key components of miRNA repressive complexes in animal cells. The aim of this project is to understand the precise molecular function of GW182 proteins in the miRNA pathway.