The ELAV protein HuD stimulates cap-dependent translation in a Poly(A)- and eIF4A-dependent manner.
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.
Fukao
Akira
A
Department of Biology, Kobe University, Rokkodaicho, Nada-ku, Japan.
Sasano
Yumi
Y
Imataka
Hiroaki
H
Inoue
Kunio
K
Sakamoto
Hiroshi
H
Sonenberg
Nahum
N
Thoma
Christian
C
Fujiwara
Toshinobu
T
D000595:Amino Acid Sequence; D000818:Animals; D051959:ELAV Proteins / Q000235:genetics / Q000378:metabolism*; D000067779:ELAV-Like Protein 4; D004742:Enhancer Elements, Genetic; D039601:Eukaryotic Initiation Factor-4A / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000502:physiology; D016716:PC12 Cells; D014176:Protein Biosynthesis; D012315:RNA Caps / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; C498011:Elavl4 protein, mouse; D012315:RNA Caps; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D039601:Eukaryotic Initiation Factor-4A