双链RNA结合蛋白RDE-4与RDE-1、DCR-1和一种DExH盒解旋酶相互作用，以指导秀丽隐杆线虫中的RNA干扰。

The dsRNA binding protein RDE-4 interacts with RDE-1, DCR-1, and a DExH-box helicase to direct RNAi in C. elegans.

作者信息

Tabara Hiroaki, Yigit Erbay, Siomi Haruhiko, Mello Craig C

机构信息

Program in Molecular Medicine, University of Massachusetts Meidcal School, Worcester, MA 1605, USA.

出版信息

Cell. 2002 Jun 28;109(7):861-71. doi: 10.1016/s0092-8674(02)00793-6.

DOI:10.1016/s0092-8674(02)00793-6

PMID:12110183

Abstract

Double-stranded (ds) RNA induces potent gene silencing, termed RNA interference (RNAi). At an early step in RNAi, an RNaseIII-related enzyme, Dicer (DCR-1), processes long-trigger dsRNA into small interfering RNAs (siRNAs). DCR-1 is also required for processing endogenous regulatory RNAs called miRNAs, but how DCR-1 recognizes its endogenous and foreign substrates is not yet understood. Here we show that the C. elegans RNAi pathway gene, rde-4, encodes a dsRNA binding protein that interacts during RNAi with RNA identical to the trigger dsRNA. RDE-4 protein also interacts in vivo with DCR-1, RDE-1, and a conserved DExH-box helicase. Our findings suggest a model in which RDE-4 and RDE-1 function together to detect and retain foreign dsRNA and to present this dsRNA to DCR-1 for processing.

摘要

双链（ds）RNA可诱导强大的基因沉默，即RNA干扰（RNAi）。在RNAi的早期阶段，一种与RNaseIII相关的酶——Dicer（DCR-1），会将长链触发dsRNA加工成小干扰RNA（siRNA）。DCR-1对于加工称为miRNA的内源性调控RNA也是必需的，但DCR-1如何识别其内源和外源底物尚不清楚。在此我们表明，秀丽隐杆线虫RNAi途径基因rde-4编码一种dsRNA结合蛋白，该蛋白在RNAi过程中与与触发dsRNA相同的RNA相互作用。RDE-4蛋白在体内还与DCR-1、RDE-1以及一种保守的DExH盒解旋酶相互作用。我们的研究结果提出了一个模型，其中RDE-4和RDE-1共同发挥作用，以检测和保留外源dsRNA，并将这种dsRNA呈递给DCR-1进行加工。