Phosphorylation Switches the General Splicing Repressor SRp38 to a Sequence-specific Activator

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2008 Sep 17

PMID 18794844

Citations 53

Authors

Ying Feng

Mo Chen

James L Manley

Affiliations

Soon will be listed here.

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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