Directional Phosphorylation and Nuclear Transport of the Splicing Factor SRSF1 Is Regulated by an RNA Recognition Motif

Directional Phosphorylation and Nuclear Transport of the Splicing Factor SRSF1 Is Regulated by an... Multisite phosphorylation is required for the biological function of serine–arginine (SR) proteins, a family of essential regulators of mRNA splicing. These modifications are catalyzed by serine–arginine protein kinases (SRPKs) that phosphorylate numerous serines in arginine–serine-rich (RS) domains of SR proteins using a directional, C-to-N-terminal mechanism. The present studies explore how SRPKs govern this highly biased phosphorylation reaction and investigate biological roles of the observed directional phosphorylation mechanism. Using NMR spectroscopy with two separately expressed domains of SRSF1, we showed that several residues in the RNA-binding motif 2 interact with the N-terminal region of the RS domain (RS1). These contacts provide a structural framework that balances the activities of SRPK1 and the protein phosphatase PP1, thereby regulating the phosphoryl content of the RS domain. Disruption of the implicated intramolecular RNA-binding motif 2–RS domain interaction impairs both the directional phosphorylation mechanism and the nuclear translocation of SRSF1 demonstrating that the intrinsic phosphorylation bias is obligatory for SR protein biological function. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Molecular Biology Elsevier

Directional Phosphorylation and Nuclear Transport of the Splicing Factor SRSF1 Is Regulated by an RNA Recognition Motif

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Publisher
Elsevier
Copyright
Copyright © 2016 Elsevier Ltd
ISSN
0022-2836
D.O.I.
10.1016/j.jmb.2016.04.009
Publisher site
See Article on Publisher Site

Abstract

Multisite phosphorylation is required for the biological function of serine–arginine (SR) proteins, a family of essential regulators of mRNA splicing. These modifications are catalyzed by serine–arginine protein kinases (SRPKs) that phosphorylate numerous serines in arginine–serine-rich (RS) domains of SR proteins using a directional, C-to-N-terminal mechanism. The present studies explore how SRPKs govern this highly biased phosphorylation reaction and investigate biological roles of the observed directional phosphorylation mechanism. Using NMR spectroscopy with two separately expressed domains of SRSF1, we showed that several residues in the RNA-binding motif 2 interact with the N-terminal region of the RS domain (RS1). These contacts provide a structural framework that balances the activities of SRPK1 and the protein phosphatase PP1, thereby regulating the phosphoryl content of the RS domain. Disruption of the implicated intramolecular RNA-binding motif 2–RS domain interaction impairs both the directional phosphorylation mechanism and the nuclear translocation of SRSF1 demonstrating that the intrinsic phosphorylation bias is obligatory for SR protein biological function.

Journal

Journal of Molecular BiologyElsevier

Published: Jun 5, 2016

References

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