ATP-dependent human RISC assembly pathways

被引：265

作者：

Yoda, Mayuko ^{[1
,2
]}

Kawamata, Tomoko ^{[1
,2
]}

Paroo, Zain ^{[3
]}

Ye, Xuecheng ^{[3
]}

Iwasaki, Shintaro ^{[1
,2
]}

Liu, Qinghua ^{[3
]}

Tomari, Yukihide ^{[1
,2
,4
]}

机构：

[1] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo, Japan

[2] Univ Tokyo, Dept Med Genome Sci, Bunkyo Ku, Tokyo, Japan

[3] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA

[4] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol, Kawaguchi, Saitama, Japan

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2010年 / 17卷 / 01期

关键词：

EMBRYONIC STEM-CELLS; SMALL SILENCING RNAS; ARGONAUTE PROTEINS; PASSENGER-STRAND; MESSENGER-RNAS; GUIDE STRAND; DROSOPHILA; COMPLEXES; SIRNA; CLEAVAGE;

D O I：

10.1038/nsmb.1733

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The assembly of RNA-induced silencing complex (RISC) is a key process in small RNA-mediated gene silencing. In humans, small interfering RNAs (siRNAs) and microRNAs (miRNAs) are incorporated into RISCs containing the Argonaute (AGO) subfamily proteins Ago1-4. Previous studies have proposed that, unlike Drosophila melanogaster RISC assembly pathways, human RISC assembly is coupled with dicing and is independent of ATP. Here we show by careful reexamination that, in humans, RISC assembly and dicing are uncoupled, and ATP greatly facilitates RISC loading of small-RNA duplexes. Moreover, all four human AGO proteins show remarkably similar structural preferences for small-RNA duplexes: central mismatches promote RISC loading, and seed or 3'-mid (guide position 12-15) mismatches facilitate unwinding. All these features of human AGO proteins are highly reminiscent of fly Ago1 but not fly Ago2.

引用

页码：17 / U29

页数：8

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