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EMBO J. 2011 Nov 25;30(24):4998-5009. doi: 10.1038/emboj.2011.426.

PABP is not essential for microRNA-mediated translational repression and deadenylation in vitro.

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Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo, Japan.


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.

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