Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways.

By K. Okamura, A. Ishizuka, H. Siomi, M. Siomi. Genes & Development, 2004

827 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/098542871560825e9daae903e868c1e86c6b02be

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Citations in the corpus

mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexes. (2006, background): “This is consistent with the observation that depletion of GW182 does not affect siRNA-guided mRNA cleavage or RNAi, which is mediated exclusively by AGO2 in Drosophila (Okamura et al. 2004; Miyoshi et al. 2005; Rehwinkel et al. 2005).”
Perspective: machines for RNAi. (2005, background): “2004b) because Ago2 is required for siRNA unwinding (Okamura et al. 2004).”
Specific association of Piwi with rasiRNAs derived from retrotransposon and heterochromatic regions in the Drosophila genome. (2006, background): “Our data suggest a novel, third kind of gene silencing pathway in Drosophila, following two distinct gene silencing pathways mediated by AGO1-miRNAs and AGO2-siRNAs (Okamura et al. 2004).”
Principles of MicroRNA–Target Recognition (2005, neutral): “[8,9,10,11,12,13,14,15].”
Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. (2005, background): “…association of Ago proteins with Dicer both in vitro and in purifications from different organisms, including Drosophila (Hammond et al., 2001, Okamura et al., 2004, Pham et al., 2004, Jiang et al., 2005, Saito et al., 2005), C. elegans (Tabara et al., 2002), and humans (Tahbaz et al., 2004,…”
Mechanisms of gene silencing by double-stranded RNA (2004, background): “melanogaster revealed that AGO1 is required for miRNA accumulation whereas AGO2 is required for siRNA-triggered mRNA degradatio”
The neuronal microRNA system (2006, background): “Drosophila embryos that lack AGO2 have defects in siRNA-directed RNAi pathways, but can undergo miRNA-directed target RNA cleavage, whereas AGO1 is dispensable for siRNA-directed RNA cleavage, but is required for miRNA-directed target RNA cleavag”
Illuminating the silence: understanding the structure and function of small RNAs (2007, background): “Target accessibility and RISC efficiency AGO2 has recently been identified as the catalytic engine of RNA”
Sorting of small RNAs into Arabidopsis argonaute complexes is directed by the 5' terminal nucleotide. (2008, background): “A similar mechanism has also been proposed for loading Drosophila miRNAs into Ago1-RISC, but the proteins facilitating miRNA loading remain to be identified (Okamura et al., 2004).”