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

P 体成分 GW182 在 MICRORNA 功能中的作用

• 批准号: 7420742
• 负责人: Gregory J Hannon
• 金额: $ 0.29万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-20 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7420742
• 关键词: microRNAs; proteins; role

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.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，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）定向的mRNA切割1。因此，microrna抑制其靶标的机制仍然是难以捉摸的。最近，RNAi关键效应组分Argonaute蛋白及其靶mrna被证明可定位于称为p -小体或gw -小体的细胞质病灶2,3。在这里，我们发现Argonaute蛋白与一个关键的P-/ gw -体亚基GW182发生物理相互作用。GW182的沉默使驻留的P-/ gw -体蛋白脱位，并损害microRNA报告蛋白的沉默。此外，阻止Argonaute蛋白在P-/ gw小体中定位的突变阻止mrna的翻译抑制，即使Argonaute以不依赖sirna的方式与靶标相连。因此，我们的研究结果支持细胞质p体与microRNA抑制靶mRNA表达的能力之间的功能联系。