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Cellular differentiation state modulates the mRNA export activity of SR proteins
Valentina Botti1, François McNicoll2, Michaela C Steiner3
1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT.
The Journal of Cell Biology
|June 9, 2017
Summary
SR proteins regulate gene expression. In pluripotent cells, SRSF5 protein shuttling is enhanced by modifications, boosting pluripotency factor export. Differentiation reduces this shuttling activity.
Area of Science:
- Molecular and Cellular Biology
- Gene Regulation
- Post-translational Modifications
Background:
- SR proteins are key regulators of nuclear pre-mRNA processing, mRNA export, and translation.
- Understanding the cellular dynamics and regulation of SR proteins is crucial for deciphering gene expression control.
Purpose of the Study:
- To investigate the differential nucleocytoplasmic shuttling of SR proteins in various cell types.
- To elucidate the mechanisms regulating SR protein shuttling and its role in cellular pluripotency.
Main Methods:
- Development of a quantitative assay for measuring nucleocytoplasmic shuttling of SR proteins.
- Application of individual-resolution cross-linking and immunoprecipitation (iCLIP) combined with mass spectrometry.
- Analysis of SR protein binding to specific transcripts and assessment of mRNA levels upon protein depletion or overexpression.
Main Results:
- SRSF2 and SRSF5 exhibit poor shuttling in HeLa cells but significant shuttling in pluripotent murine P19 cells.
- Elevated arginine methylation of SRSF5 and reduced phosphorylation of SRSF2 enhance SRSF5 shuttling in P19 cells.
- SRSF5 binds pluripotency-specific transcripts (e.g., Lin28a, Pou5f1/Oct4) in the cytoplasm, influencing their export and expression.
- Neural differentiation of P19 cells drastically reduces SRSF5 shuttling.
Conclusions:
- Post-translational modifications of SR proteins, specifically arginine methylation and phosphorylation, dynamically regulate their mRNA export activities.
- Enhanced SRSF5 shuttling is essential for maintaining pluripotency by facilitating the export of key pluripotency factors.
- SR protein shuttling patterns distinguish pluripotent cells from differentiated cells, highlighting a role in cell fate determination.
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