Journal
EMBO JOURNAL
Volume 30, Issue 24, Pages 4998-5009Publisher
WILEY
DOI: 10.1038/emboj.2011.426
Keywords
Argonaute; deadenylation; GW182; microRNA; translational repression
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Funding
- Japan Ministry of Education, Culture, Sports, Science and Technology
- The International Human Frontier Science Program Organization
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MicroRNAs silence their complementary target genes via formation of the RNA-induced silencing complex (RISC) that contains an Argonaute (Ago) protein at its core. It was previously proposed that GW182, an Ago-associating protein, directly binds to poly(A)-binding protein (PABP) and interferes with its function, leading to silencing of the target mRNAs. Here we show that Drosophila Ago1-RISC induces silencing via two independent pathways: shortening of the poly(A) tail and pure repression of translation. Our data suggest that although PABP generally modulates poly(A) length and translation efficiency, neither PABP function nor GW182-PABP interaction is a prerequisite for these two silencing pathways. Instead, we propose that each of the multiple functional domains within GW182 has a potential for silencing, and yet they need to act together in the context of full-length GW182 to exert maximal silencing. The EMBO Journal (2011) 30, 4998-5009. doi: 10.1038/emboj.2011.426; Published online 25 November 2011
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