Hsc70/Hsp90 Chaperone Machinery Mediates ATP-Dependent RISC Loading of Small RNA Duplexes
Hsc70/Hsp90 Chaperone Machinery Mediates ATP-Dependent RISC Loading of Small RNA Duplexes
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DOI：
10.1016/j.molcel.2010.05.015
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发表时间：
2010-07-30
期刊：
影响因子：
16
通讯作者：
Tomari, Yukihide
中科院分区：
文献类型：
--
作者：
Iwasaki, Shintaro;Kobayashi, Maki;Tomari, Yukihide
小沉默RNAs-小干扰RNAs(SiRNAs)或microRNAs(MiRNAs)-直接转录后基因沉默其mRNA靶标，作为RNA诱导沉默复合体(RISC)的指南。SiRNAs和miRNAs生来都是双链的。令人惊讶的是，将这些小RNA双链加载到RISC的核心成分ArgAerte蛋白质中需要ATP，而分离ArgAerte内的两条小RNA链则不需要。在这里，我们证明了Hsc70/Hsp90伴侣机制是必要的，以装载小RNA双链到ArgAerte蛋白质中，但不是为了随后的链分离或靶切割。我们设想，伴侣机制使用ATP并介导AGO蛋白的构象开放，从而使它们能够接收巨大的小RNA双链。我们的数据表明，伴侣机制可能是RISC组装途径的驱动力。
Small silencing RNAs-small interfering RNAs (siRNAs) or microRNAs (miRNAs)-direct posttranscriptional gene silencing of their mRNA targets as guides for the RNA-induced silencing complex (RISC). Both siRNAs and miRNAs are born double stranded. Surprisingly, loading these small RNA duplexes into Argonaute proteins, the core components of RISC, requires ATP, whereas separating the two small RNA strands within Argonaute does not. Here we show that the Hsc70/Hsp90 chaperone machinery is required to load small RNA duplexes into Argonaute proteins, but not for subsequent strand separation or target cleavage. We envision that the chaperone machinery uses ATP and mediates a conformational opening of Ago proteins so that they can receive bulky small RNA duplexes. Our data suggest that the chaperone machinery may serve as the driving force for the RISC assembly pathway.