Cell Stress Modulates the Function of Splicing Regulatory Protein Rbm4 in Translation Control
Resource
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA v.104 n.7 pp.2235-2240
Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Journal Volume
v.104
Journal Issue
n.7
Pages
2235-2240
Date Issued
2007
Date
2007
Author(s)
Lin, J.-C.
Hsu, M.
Tarn, W.-Y.
Abstract
RNA-binding motif protein 4 (RBM4) plays a regulatory role in alternative splicing of precursor mRNA. We show here that cell stress such as arsenite exposure induces phosphorylation of RBM4 at serine 309 and also drives its cytoplasmic accumulation and targeting to stress granule via the MKK3/6-p38 signaling pathway. Accordingly, RBM4 suppresses cap- dependent translation in a cis-element- dependent manner. However, RBM4 concomitantly activates internal ribosome entry site (IRES)-mediated translation likely by promoting the association of translation initiation factor eIF4A with IRES-containing mRNAs. Overexpression of RBM4 therefore mimics the effect of cell stress-induced signaling on translation initiation control. Whereas arsenite treatment promotes RBM4 loading onto IRES mRNAs and enhances RBM4-eIF4A interactions, a nonphosphorylatable mutant of RBM4 was unresponsive to arsenite stress and failed to activate IRES-mediated translation. Thus, our results uncover a previously unrecognized paradigm for the RNA-binding protein RIBM4 in its phosphorylation-modulated dual action as a suppressor of cap-dependent and enhancer of IRES-mediated translation in response to stress signals.
Subjects
cell stress
eIF4A
internal ribosome entry site
phosphorylation
splicing factor