GSBS Student Publications

Title

Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes

Publication Date

2005-11-08

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Document Type

Article

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

In the Drosophila and mammalian RNA interference pathways, siRNAs direct the protein Argonaute2 (Ago2) to cleave corresponding mRNA targets, silencing their expression. Ago2 is the catalytic component of the RNAi enzyme complex, RISC. For each siRNA duplex, only one strand, the guide, is assembled into the active RISC; the other strand, the passenger, is destroyed. An ATP-dependent helicase has been proposed first to separate the two siRNA strands, then the resulting single-stranded guide is thought to bind Ago2. Here, we show that Ago2 instead directly receives the double-stranded siRNA from the RISC assembly machinery. Ago2 then cleaves the siRNA passenger strand, thereby liberating the single-stranded guide. For siRNAs, virtually all RISC is assembled through this cleavage-assisted mechanism. In contrast, passenger-strand cleavage is not important for the incorporation of miRNAs that derive from mismatched duplexes.

DOI of Published Version

10.1016/j.cell.2005.08.044

Source

Cell. 2005 Nov 18;123(4):607-20. Epub 2005 Nov 3. Link to article on publisher's site

Journal/Book/Conference Title

Cell

Related Resources

Link to article in PubMed

PubMed ID

16271386

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