EMBO Conference on Protein Synthesis and Translational Control

AKIRA FUKAO
Enhancement of cap-dependent translation by the ELAV protein HuD:
A novel function of HuD which is eIF4A- and poly(A)-dependent
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Speaker Abstracts
Akira Fukao 1, Kunio Inoue 1, Hiroshi Sakamoto 1, Yumi Sasano 1, Toshinobu Fujiwara 1,
Nahum Sonenberg 2, Christian Thoma 3, Hiroaki Imataka 4
1 Kobe University, Japan
2 McGill University, Canada
3 University Hospital of Freiburg, Germany
4 University of Hyogo, Japan
RNA-binding proteins have emerged as specific regulators of gene expression. The
RNA-binding protein HuD, one member of the neuronal Hu family of proteins promotes
neuronal differentiation by an unknown mechanism. Here we show that HuD enhances
translation. Translation stimulation by HuD requires both a poly(A) tail at the 3´ end of mRNAs
and a 5´ m7G cap structure. We also show that HuD associates with the cap-binding complex
via direct binding to eIF4A and poly(A) and that the poly(A) and eIF4A 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 also find that these molecular interactions are
important for HuD-induced neurite outgrowth in PC12 cells. Our results reveal a novel function
of HuD in translation, which might explain at least in part how HuD promotes the induction of
neuronal differentiation.