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Mammalian miRNA RISC recruits CAF1 and PABP to affect PABP-Dependent Deadenylation

Fabian, Marc R, Mathonnet, Géraldine, Sundermeier, Thomas, Mathys, Hansruedi, Zipprich, Jakob T, Svitkin, Yuri V, Rivas, Fabiola, Jinek, Martin, Wohlschlegel, James, Doudna, Jennifer A, Chen, Chyi-Ying A, Shyu, Ann-Bin, Yates, John R, Hannon, Gregory J, Filipowicz, Witold, Duchaine, Thomas F and Sonenberg, Nahum (2009) Mammalian miRNA RISC recruits CAF1 and PABP to affect PABP-Dependent Deadenylation. Molecular Cell, 35 (6). pp. 868-880. ISSN 1097-2765


MicroRNAs (miRNAs) inhibit mRNA expression in general by base pairing to the 3'UTR of target mRNAs and consequently inhibiting translation and/or initiating poly(A) tail deadenylation and mRNA destabilization. Here we examine the mechanism and kinetics of miRNA-mediated deadenylation in mouse Krebs-2 ascites extract. We demonstrate that miRNA-mediated mRNA deadenylation occurs subsequent to initial translational inhibition, indicating a two-step mechanism of miRNA action, which serves to consolidate repression. We show that a let-7 miRNA-loaded RNA-induced silencing complex (miRISC) interacts with the poly(A)-binding protein (PABP) and the CAF1 and CCR4 deadenylases. In addition, we demonstrate that miRNA-mediated deadenylation is dependent upon CAF1 activity and PABP, which serves as a bona fide miRNA coactivator. Importantly, we present evidence that GW182, a core component of the miRISC, directly interacts with PABP via its C-terminal region and that this interaction is required for miRNA-mediated deadenylation.

Item Type: Article
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Additional Information: Author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords: RNA; proteins
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Date Deposited: 22 Feb 2010 11:49
Last Modified: 31 Jan 2013 00:47


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