The Argonautes

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Abstract
RNA interference (RNAi) has been greatly exploited in recent years as an increasingly effective tool to study gene functionby gene silencing. The introduction of exogenous double-stranded RNA (dsRNA) into a cell can trigger this gene silencingprocess. An RNase III family enzyme, Dicer, initiates silencing by releasing approximately 20 base duplexes, with 2-nucleotide 3' overhangs called siRNAs. The RNAi pathway also mediates the function of endogenous, noncoding regulatoryRNAs called miRNAs. Both miRNAs and siRNAs guide substrate selection by similar if not identical effector complexescalled RISCs. These contain single-stranded versions of the small RNA and additional protein components. Of those, the signatureelement, at the heart of all RISCs, is a member of the Argonaute family of proteins. Our structural and biochemicalstudies on Argonaute identified this protein as Slicer, the enzyme in RISC that cleaves the mRNA as directed by the siRNA.The role of the Argonautes as Slicers and non-Slicers is discussed.