Phosphorylation switches the general splicing repressor SRp38 to a sequence-specific activator.
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.
Feng
Ying
Y
Department of Biological Sciences, Columbia University, 1212 Amsterdam Avenue, New York, New York 10027, USA.
Chen
Mo
M
Manley
James L
JL
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002645:Chickens; D005091:Exons / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000378:metabolism; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000378:metabolism; D017381:Spliceosomes / Q000378:metabolism; D013379:Substrate Specificity
D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; D017413:Ribonucleoprotein, U2 Small Nuclear
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