ミシマ ユウイチロウ   Mishima Yuichiro
  三嶋 雄一郎
   所属   京都産業大学  生命科学部 先端生命科学科
   職種   准教授
言語種別 英語
発行・発表の年月 2014/10
形態種別 研究論文
査読 査読あり
標題 MicroRNAs Trigger Dissociation of eIF4AI and eIF4AII from Target mRNAs in Humans
執筆形態 その他
掲載誌名 MOLECULAR CELL
出版社・発行元 CELL PRESS
巻・号・頁 56(1),pp.79-89
著者・共著者 Akira Fukao,Yuichiro Mishima,Naoki Takizawa,Shigenori Oka,Hiroaki Imataka,Jerry Pelletier,Nahum Sonenberg,Christian Thoma,Toshinobu Fujiwara
概要 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.
DOI 10.1016/j.molcel.2014.09.005
ISSN 1097-2765/1097-4164
PMID 25280105