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Downloaded from genesdev.cshlp.org on October 16, 2021 - Published by Cold Spring Harbor Laboratory Press Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways Katsutomo Okamura, Akira Ishizuka, Haruhiko Siomi, and Mikiko C. Siomi Institute for Genome Research, University of Tokushima, Tokushima 770-8503, Japan In mammalian cells, both microRNAs (miRNAs) and small interfering RNAs (siRNAs) are thought to be loaded into the same RNA-induced silencing complex (RISC), where they guide mRNA degradation or translation silencing depending on the complementarity of the target. In Drosophila, Argonaute2 (AGO2) was identified as part of the RISC complex. Here we show that AGO2 is an essential component for siRNA-directed RNA interference (RNAi) response and is required for the unwinding of siRNA duplex and in consequence assembly of siRNA into RISC in Drosophila embryos. However, Drosophila embryos lacking AGO2, which are siRNA-directed RNAi-defective, are still capable of miRNA-directed target RNA cleavage. In contrast, Argonaute1 (AGO1), another Argonaute protein in fly, which is dispensable for siRNA-directed target RNA cleavage, is required for mature miRNA production that impacts on miRNA-directed RNA cleavage. The association of AGO1 with Dicer-1 and pre-miRNA also suggests that AGO1 is involved in miRNA biogenesis. Our findings show that distinct
Genes & Development – Unpaywall
Published: Jul 1, 2004
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