A ROLE FOR THE P-BODY COMPONENT GW182 IN MICRORNA FUNCTION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 在动物中，大多数microRNA通过RNA干扰（RNAi）机制调节基因表达，而不诱导小干扰RNA（siRNA）指导的mRNA切割1。因此，microRNA抑制其靶标的机制仍然难以捉摸。最近，Argonaute蛋白，这是关键的RNAi效应成分，和他们的目标mRNA显示定位于细胞质病灶称为P-体或GW-体2，3。在这里，我们表明，Argonaute蛋白物理相互作用的关键P-/GW-体亚基，GW 182。GW 182的沉默使驻留的P-/GW-体蛋白离域并损害microRNA报告基因的沉默。此外，阻止Argonaute蛋白定位于P-/GW-体的突变阻止mRNA的翻译抑制，即使Argonaute以siRNA非依赖性方式与其靶标连接。因此，我们的研究结果支持细胞质P体和microRNA抑制靶mRNA表达的能力之间的功能联系。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In animals, the majority of microRNAs regulate gene expression through the RNA interference (RNAi) machinery without inducing small-interfering RNA (siRNA)-directed mRNA cleavage1. Thus, the mechanisms by which microRNAs repress their targets have remained elusive. Recently, Argonaute proteins, which are key RNAi effector components, and their target mRNAs were shown to localize to cytoplasmic foci known as P-bodies or GW-bodies2, 3. Here, we show that the Argonaute proteins physically interact with a key P-/GW-body subunit, GW182. Silencing of GW182 delocalizes resident P-/GW-body proteins and impairs the silencing of microRNA reporters. Moreover, mutations that prevent Argonaute proteins from localizing in P-/GW-bodies prevent translational repression of mRNAs even when Argonaute is tethered to its target in a siRNA-independent fashion. Thus, our results support a functional link between cytoplasmic P-bodies and the ability of a microRNA to repress expression of a target mRNA.