Abstract
SRp38 is an atypical SR protein that functions as a general splicing repressor when dephosphorylated. We now show that phosphorylated SRp38 functions as a sequence-specific splicing activator. Unlike characterized splicing activators, SRp38 functions in the absence of other SR proteins but requires a cofactor for activity. SRp38 was able to induce formation of splicing complex A in the absence of the cofactor, but this factor was necessary for progression to complexes B and C. Mechanistically, SRp38 strengthens the ability of the U1 and U2 small nuclear ribonucleoproteins to stably recognize the pre-mRNA. Extending these findings, analysis of alternative splicing of pre-mRNA encoding the glutamate receptor B revealed that SRp38 alters its splicing pattern in a sequence-specific manner. Together, our data demonstrate that SRp38, in addition to its role as a splicing repressor, can function as an unusual sequence-specific splicing activator.
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Acknowledgements
We thank R. Lührmann (Max Planck Institute for Biophysical Chemistry, Germany) for providing purified U1 and U2 snRNP, T. Kashima (Columbia University, New York) for SR proteins and C. Shin (Columbia University, New York) for His-dSRp38. We thank A. Yang for help with the manuscript. We also thank members of the Manley laboratory for helpful discussions and comments. This work was supported by the US National Institutes of Health grant NIH GM48259.
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Feng, Y., Chen, M. & Manley, J. Phosphorylation switches the general splicing repressor SRp38 to a sequence-specific activator. Nat Struct Mol Biol 15, 1040–1048 (2008). https://doi.org/10.1038/nsmb.1485
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DOI: https://doi.org/10.1038/nsmb.1485
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