Cell stress modulates the function of splicing regulatory protein RBM4 in translation control

Jung Chun Lin, Min Hsu, Woan Yuh Tarn

Research output: Contribution to journalArticle

61 Citations (Scopus)

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 MKK 3/6-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 elF4A 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-elF4A 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 RBM4 in its phosphorylation-modulated dual action as a suppressor of cap-dependent and enhancer of IRES-mediated translation in response to stress signals.

Original languageEnglish
Pages (from-to)2235-2240
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number7
DOIs
Publication statusPublished - Feb 13 2007
Externally publishedYes

Fingerprint

Protein Splicing
RNA-Binding Proteins
Phosphorylation
RNA-Binding Motifs
Peptide Initiation Factors
Messenger RNA
RNA Precursors
Alternative Splicing
Protein Binding
Serine
Internal Ribosome Entry Sites

Keywords

  • Cell stress
  • elF4A
  • Internal ribosome entry site
  • Phosphorylation
  • Splicing factor

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Cell stress modulates the function of splicing regulatory protein RBM4 in translation control. / Lin, Jung Chun; Hsu, Min; Tarn, Woan Yuh.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 7, 13.02.2007, p. 2235-2240.

Research output: Contribution to journalArticle

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