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

Jung-Chun Lin1, Min Hsu, Woan-Yuh Tarn

  • 1Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.

Proceedings of the National Academy of Sciences of the United States of America
|February 8, 2007
PubMed

Insights

Cell stress triggers RNA-binding motif protein 4 (RBM4) phosphorylation, impacting translation. Phosphorylated RBM4 suppresses cap-dependent translation while enhancing internal ribosome entry site (IRES)-mediated translation.

Area of Science:

  • Molecular Biology
  • Cellular Stress Response
  • RNA Biology

Background:

  • RNA-binding motif protein 4 (RBM4) regulates alternative splicing.
  • Cellular stress pathways are crucial for cell survival and adaptation.
  • Translation initiation mechanisms control protein synthesis.

Purpose of the Study:

  • To investigate the role of RBM4 in cellular stress response.
  • To elucidate the impact of RBM4 phosphorylation on translation control.
  • To understand the dual function of RBM4 in cap-dependent and IRES-mediated translation.

Main Methods:

  • Arsenite exposure to induce cell stress.
  • Analysis of RBM4 phosphorylation at serine 309.
  • Studying RBM4 localization to stress granules.
  • Investigating RBM4 interaction with translation initiation factor eIF4A.
  • Assessing RBM4 effects on cap-dependent and IRES-mediated translation.

Main Results:

  • Cell stress induces RBM4 phosphorylation, cytoplasmic accumulation, and stress granule targeting via the MKK(3/6)-p38 pathway.
  • RBM4 suppresses cap-dependent translation but enhances IRES-mediated translation.
  • Phosphorylation is critical for RBM4's stress-induced activation of IRES-mediated translation and eIF4A association.

Conclusions:

  • RBM4 exhibits a phosphorylation-dependent dual role in translation control during cellular stress.
  • RBM4 acts as a suppressor of cap-dependent translation and an enhancer of IRES-mediated translation.
  • This uncovers a novel mechanism for RNA-binding proteins in stress-induced translational regulation.

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