Mammalian miRNA RISC recruits CAF1 and PABP to affect PABP-dependent deadenylation. Export

@article{citeulike:5666855, abstract = {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.}, author = {Fabian, Marc R. and Mathonnet, G\'{e}raldine and Sundermeier, Thomas and Mathys, Hansruedi and Zipprich, Jakob T. and Svitkin, Yuri V. and Rivas, Fabiola and Jinek, Martin and Wohlschlegel, James and Doudna, Jennifer A. and Chen, Chyi-Ying Y. and Shyu, Ann-Bin B. and Yates, John R. and Hannon, Gregory J. and Filipowicz, Witold and Duchaine, Thomas F. and Sonenberg, Nahum}, citeulike-article-id = {5666855}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.molcel.2009.08.004}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S1097276509005504}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19716330}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19716330}, day = {24}, doi = {10.1016/j.molcel.2009.08.004}, issn = {1097-4164}, journal = {Molecular cell}, keywords = {gene\_regulation, mammalian, mirna, polya, posttranscriptional, regulation, transcript}, month = {September}, number = {6}, pages = {868--880}, posted-at = {2009-10-25 20:34:07}, priority = {2}, title = {Mammalian miRNA RISC recruits CAF1 and PABP to affect PABP-dependent deadenylation.}, url = {http://dx.doi.org/10.1016/j.molcel.2009.08.004}, volume = {35}, year = {2009} }

TY - JOUR ID - citeulike:5666855 L3 - citeulike-article-id:5666855 N2 - 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. IS - 6 JF - Molecular cell SN - 1097-4164 EP - 880 TI - Mammalian miRNA RISC recruits CAF1 and PABP to affect PABP-dependent deadenylation. VL - 35 SP - 868 KW - gene_regulation KW - mammalian KW - mirna KW - polya KW - posttranscriptional KW - regulation KW - transcript AU - Fabian, Marc AU - Mathonnet, Géraldine AU - Sundermeier, Thomas AU - Mathys, Hansruedi AU - Zipprich, Jakob AU - Svitkin, Yuri AU - Rivas, Fabiola AU - Jinek, Martin AU - Wohlschlegel, James AU - Doudna, Jennifer AU - Chen, Chyi-Ying AU - Shyu, Ann-Bin AU - Yates, John AU - Hannon, Gregory AU - Filipowicz, Witold AU - Duchaine, Thomas AU - Sonenberg, Nahum PY - 2009/09/24/ UR - http://dx.doi.org/10.1016/j.molcel.2009.08.004 ER -