The ELAV Protein HuD Stimulates Cap-Dependent Translation in a Poly(A)- and eIF4A-Dependent Manner

被引：84

作者：

Fukao, Akira ^{[2
]}

Sasano, Yumi ^{[3
,8
]}

Imataka, Hiroaki ^{[4
]}

Inoue, Kunio ^{[2
]}

Sakamoto, Hiroshi ^{[2
]}

Sonenberg, Nahum ^{[5
,6
]}

Thoma, Christian ^{[1
]}

Fujiwara, Toshinobu ^{[3
,7
]}

机构：

[1] Univ Hosp Freiburg, Dept Med 2, D-79106 Freiburg, Germany

[2] Kobe Univ, Grad Sch Sci, Dept Biol, Nada Ku, Kobe, Hyogo 6578501, Japan

[3] Kobe Univ, Grad Sch Engn, Dept Sci & Chem Engn, Nada Ku, Kobe, Hyogo 6578501, Japan

[4] Univ Hyogo, Grad Sch Engn, Dept Mat Sci & Chem, Himeji, Hyogo 6712280, Japan

[5] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada

[6] McGill Univ, McGill Canc Ctr, Montreal, PQ H3G 1Y6, Canada

[7] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol, Kawaguchi, Saitama 3320012, Japan

[8] NAGASE & CO LTD, Ctr Res & Dev, Drug Discovery Support Technol Dev Team, Nishi Ku, Kobe, Hyogo 6512241, Japan

来源：

MOLECULAR CELL | 2009年 / 36卷 / 06期

关键词：

RNA-BINDING PROTEINS; INITIATION-FACTOR; 4B; NERVE GROWTH-FACTOR; AU-RICH ELEMENT; MESSENGER-RNA; EUKARYOTIC TRANSLATION; NEURONAL DIFFERENTIATION; HELICASE ACTIVITY; POLY(A)-BINDING PROTEIN; MAMMALIAN TRANSLATION;

D O I：

10.1016/j.molcel.2009.11.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The RNA-binding protein HuD promotes neuronal differentiation by an unknown mechanism. Here we identify an enhancer function of HuD in translation. Translation stimulation by HuD requires both a 3' poly(A) tail and a 5' m(7)G cap structure. We also show that HuD directly interacts with eIF4A. This interaction and the poly(A)-binding activity of HuD are critical for its translational enhancer function because HuD-eIF4A- and HuD-poly(A)-binding mutants fail to stimulate translation. We show that translation of HCV IRES mRNA, which is eIF4A independent, is not stimulated by HuD. We also find that the eIF4A and poly(A)-binding activities of HuD are not only important for stimulating translation but also are essential for HuD-induced neurite outgrowth in PC12 cells. This example of cap-dependent translational regulation might explain at least in part how HuD triggers the induction of neuronal differentiation.

引用

页码：1007 / 1017

页数：11

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