Regulation of alternative splicing by SRrp86 through coactivation and repression of specific SR proteins.
SRrp86 is an 86-kDa member of the SR protein superfamily that is unique in that it can alter splice site selection by regulating the activity of other SR proteins. To study the function of SRrp86, inducible cell lines were created in which the concentration of SRrp86 could be varied and its effects on alternative splicing determined. Here, we show that SRrp86 can activate SRp20 and repress SC35 in a dose-dependent manner both in vitro and in vivo. These effects are apparently mediated through direct protein-protein interaction, as pull-down assays showed that SRrp86 interacts with both SRp20 and SC35. Consistent with the hypothesis that relatively modest changes in the concentration or activity of one or more splicing factors can combinatorially regulate overall splicing, protein expression patterns of SRrp86, SRp20, and SC35 reveal that each tissue maintains a unique ratio of these factors. Regulation of SR protein activity, coupled with regulated protein expression, suggest that SRrp86 may play a crucial role in determining tissue specific patterns of alternative splicing.
Barnard
Daron C
DC
Department of Molecular Biology, Vanderbilt University, Nashville, Tennessee 37235, USA.
Li
Jun
J
Peng
Rui
R
Patton
James G
JG
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D017398:Alternative Splicing; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D000068103:Serine-Arginine Splicing Factors
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D002352:Carrier Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; C458841:SREK1 protein, human; C491388:SRSF3 protein, human; C486754:Srek1 protein, rat; D000068103:Serine-Arginine Splicing Factors