RRC ID 73752
Author Okamura K, Ishizuka A, Siomi H, Siomi MC.
Title Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways.
Journal Genes Dev
Abstract 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 Argonaute proteins act at different steps of the small RNA silencing mechanism and suggest that there are inherent differences between siRNA-initiated RISCs and miRNA-initiated RISCs in Drosophila.
Volume 18(14)
Pages 1655-66
Published 2004-7-15
DOI 10.1101/gad.1210204
PII 1210204
PMID 15231716
PMC PMC478188
MeSH Animals Argonaute Proteins Base Sequence Blotting, Northern DNA Primers Drosophila / embryology* Drosophila Proteins / metabolism* Drosophila Proteins / physiology Embryo, Nonmammalian / metabolism Eukaryotic Initiation Factors MicroRNAs / biosynthesis* RNA Interference / physiology* RNA, Messenger / metabolism* RNA, Small Interfering / metabolism* RNA-Induced Silencing Complex / metabolism* RNA-Induced Silencing Complex / physiology
IF 9.527
Drosophila 10001Ab-1