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

The dsRNA binding protein RDE-4 interacts with RDE-1, DCR-1, and a DExX-box helicase to direct RNAi in C-elegans
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DOI:
10.1016/s0092-8674(02)00793-6
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发表时间:
2002-06-28
期刊:
影响因子:
64.5
通讯作者:
Mello, CC
Mello, CC
中科院分区:
生物学1区
文献类型:
--
作者:
Tabara, H;Yigit, E;Mello, CC

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双链RNA可诱导基因沉默,称为RNA干扰(RNAi)。在RNAi的早期阶段,RNaseIII相关的酶DICER(DCR-1)将长触发的dsRNA处理成小干扰RNA(SiRNAs)。DCR-1也是处理内源调控RNA所必需的,称为miRNAs,但DCR-1如何识别其内源和外源底物尚不清楚。在这里,我们证明了线虫RNAi途径基因rde-4编码一种dsRNA结合蛋白,在RNAi过程中与与触发dsRNA相同的RNA相互作用。Rde-4蛋白在体内也与DCR-1、RDE-1以及保守的DExH-box解旋酶相互作用。我们的发现提出了一种模型,在该模型中,RDE-4和RDE-1共同发挥作用,检测和保留外源dsRNA,并将该dsRNA呈现给DCR-1进行处理。
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.