Guided Tour to the Heart of RISC

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Science  25 May 2012:
Vol. 336, Issue 6084, pp. 985-986
DOI: 10.1126/science.1223549

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How do eukaryotic cells use small RNAs to control the expression levels of proteins? The answer is of interest both to basic researchers and to those harnessing RNA interference (RNAi) pathways for therapeutic applications. As laboratories around the world have steadily uncovered the complex network of RNAi components, Argonaute (Ago) proteins emerged early on as key players within a complex machinery that exists in all RNAi-competent cells. On page 1037 of this issue, Schirle and MacRae report the crystal structure of human Argonaute2 (Ago2), the flagship member of this class of multidomain enzymes (1). Together with a recently reported structure of an Argonaute protein from the budding yeast Kluyveromyces polysporus (KpAgo) (2), this work provides an exciting glimpse into the core of the molecular pathway for small RNA-mediated gene regulation and fundamental insights into structural evolution of RNAi in eukaryotes.