Anatomy of RISC: how do small RNAs and chaperones activate Argonaute proteins?

Anatomy of RISC: how do small RNAs and chaperones activate Argonaute proteins?
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DOI:
10.1002/wrna.1356
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发表时间:
2016-09
影响因子:
7.3
通讯作者:
Nakanishi, Kotaro
Nakanishi, Kotaro
中科院分区:
生物学2区
文献类型:
--
作者:
Nakanishi, Kotaro

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RNA沉默是一种真核生物特异性现象,其中microrna和小干扰RNA降解含有互补序列的信使RNA。为此,这些小RNA需要被装载到Argonaute蛋白(AGO蛋白)上,形成被称为RNA诱导沉默复合物(RISC)的效应复合物。在Hsc70/Hsp90伴侣机器的帮助下,RISC组装经历多个顺序步骤。这种组装过程的分子机制尚不清楚,尽管它们对基因沉默技术和基于RNA干扰的治疗方法的发展具有重要意义。这篇综述剖析了目前可用的AGO蛋白结构,并提出了RISC组装的模型和假设,包括未加载AGO蛋白的构象,伴侣辅助的双工加载,以及依赖于和不依赖于切片机的双工分离。在原核生物和真核生物之间的RISC性质的差异也将澄清。生物学报,2016,7:637 - 660。doi: 10.1002 / wrna.1356有关与本文相关的更多资源,请访问WIREs网站。
RNA silencing is a eukaryote‐specific phenomenon in which microRNAs and small interfering RNAs degrade messenger RNAs containing a complementary sequence. To this end, these small RNAs need to be loaded onto an Argonaute protein (AGO protein) to form the effector complex referred to as RNA‐induced silencing complex (RISC). RISC assembly undergoes multiple and sequential steps with the aid of Hsc70/Hsp90 chaperone machinery. The molecular mechanisms for this assembly process remain unclear, despite their significance for the development of gene silencing techniques and RNA interference‐based therapeutics. This review dissects the currently available structures of AGO proteins and proposes models and hypotheses for RISC assembly, covering the conformation of unloaded AGO proteins, the chaperone‐assisted duplex loading, and the slicer‐dependent and slicer‐independent duplex separation. The differences in the properties of RISC between prokaryotes and eukaryotes will also be clarified. WIREs RNA 2016, 7:637–660. doi: 10.1002/wrna.1356 For further resources related to this article, please visit the WIREs website.
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