PMID- 25280105 OWN - NLM STAT- MEDLINE DCOM- 20141229 LR - 20141004 IS - 1097-4164 (Electronic) IS - 1097-2765 (Linking) VI - 56 IP - 1 DP - 2014 Oct 2 TI - MicroRNAs trigger dissociation of eIF4AI and eIF4AII from target mRNAs in humans. PG - 79-89 LID - S1097-2765(14)00712-6 [pii] LID - 10.1016/j.molcel.2014.09.005 [doi] AB - In animals, key functions of microRNA-induced silencing complex (miRISC) are translational repression and deadenylation followed by mRNA decay. While miRISC represses translation initiation, it is poorly understood how miRISC exerts this function. Here we assessed the effect of miRISC on synergistic recruitment of translation initiation factors to target mRNAs by using direct biochemical assays. We show that miRISC promotes eIF4AI and eIF4AII release from target mRNAs prior to dissociation of eIF4E and eIF4G in a deadenylation-independent manner. Strikingly, miRISC-induced release of eIF4AI and eIF4AII from target mRNAs and miRISC-induced inhibition of cap-dependent translation can both be counteracted by the RNA-binding protein HuD via a direct interaction of HuD with eIF4A. Furthermore, the pharmacological eIF4A inhibitor silvestrol, which locks eIF4A on mRNAs, conferred resistance to miRNA-mediated translational repression. In summary, we propose that both eIF4AI and eIF4AII are functionally important targets in miRISC-mediated translation control. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Fukao, Akira AU - Fukao A AD - Laboratory of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan. FAU - Mishima, Yuichiro AU - Mishima Y AD - Institute of Molecular and Cellular Biosciences, Department of Medical Genome Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. FAU - Takizawa, Naoki AU - Takizawa N AD - Institute of Microbial Chemistry, Laboratory of Basic Biology, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan. FAU - Oka, Shigenori AU - Oka S AD - Pharma Medical Division, Life & Healthcare Products Department, Nagase & Co., Ltd., 2-2-3 Murotani, Nishi-ku, Kobe, Hyogo 651-2241, Japan. FAU - Imataka, Hiroaki AU - Imataka H AD - Department of Materials Science and Chemistry, Graduate School of Engineering, University of Hyogo, Himeji 671-2280, Japan. FAU - Pelletier, Jerry AU - Pelletier J AD - Department of Biochemistry, Department of Oncology, and The Rosalind and Morris Goodman Cancer Research Center and McGill Cancer Centre, McGill University, Montreal, QC H3G 1Y6, Canada. FAU - Sonenberg, Nahum AU - Sonenberg N AD - Department of Biochemistry, Department of Oncology, and The Rosalind and Morris Goodman Cancer Research Center and McGill Cancer Centre, McGill University, Montreal, QC H3G 1Y6, Canada. FAU - Thoma, Christian AU - Thoma C AD - Department of Medicine II, University Hospital of Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany. FAU - Fujiwara, Toshinobu AU - Fujiwara T AD - Laboratory of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan. Electronic address: tosinobu@phar.nagoya-cu.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Cell JT - Molecular cell JID - 9802571 RN - 0 (MicroRNAs) RN - 0 (RNA, Messenger) RN - 0 (RNA-Induced Silencing Complex) RN - 0 (Triterpenes) RN - 0 (silvestrol) RN - EC 2.7.7.- (Eukaryotic Initiation Factor-4A) SB - IM MH - Eukaryotic Initiation Factor-4A/antagonists & inhibitors/genetics/*metabolism MH - HEK293 Cells MH - Humans MH - MicroRNAs/*physiology MH - *Models, Genetic MH - RNA, Messenger/*metabolism MH - RNA-Induced Silencing Complex/physiology MH - Transcription Initiation, Genetic MH - Triterpenes/pharmacology EDAT- 2014/10/04 06:00 MHDA- 2014/12/30 06:00 CRDT- 2014/10/04 06:00 PHST- 2014/01/31 00:00 [received] PHST- 2014/07/18 00:00 [revised] PHST- 2014/08/28 00:00 [accepted] PHST- 2014/10/04 06:00 [entrez] PHST- 2014/10/04 06:00 [pubmed] PHST- 2014/12/30 06:00 [medline] AID - S1097-2765(14)00712-6 [pii] AID - 10.1016/j.molcel.2014.09.005 [doi] PST - ppublish SO - Mol Cell. 2014 Oct 2;56(1):79-89. doi: 10.1016/j.molcel.2014.09.005.