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- Title
ATP-dependent human RISC assembly pathways.
- Authors
Mayuko Yoda; Tomoko Kawamata; Zain Paroo; Xuecheng Ye; Iwasaki, Shintaro; Qinghua Liu; Tomari, Yukihide
- Abstract
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.
- Publication
Nature Structural & Molecular Biology, 2010, Vol 17, Issue 1, p17
- ISSN
1545-9993
- Publication type
Academic Journal
- DOI
10.1038/nsmb.1733