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Phosphorylation-dephosphorylation differentially affects activities of splicing factor ASF/SF2
1Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
The EMBO Journal
|November 3, 1998
Summary
Phosphorylation of SR protein ASF/SF2 dynamically regulates its interactions with other proteins. Dephosphorylation is not required for ASF/SF2
Area of Science:
- Molecular Biology
- RNA Splicing
- Protein Phosphorylation
Background:
- SR proteins, including ASF/SF2, are crucial splicing factors involved in both constitutive and activated splicing.
- Previous research indicated phosphorylation of ASF/SF2 is necessary for its splicing function, with dephosphorylation also potentially required for constitutive splicing.
- The dynamic interplay of phosphorylation and dephosphorylation in SR protein function remains incompletely understood.
Purpose of the Study:
- To investigate how the phosphorylation status of ASF/SF2 differentially impacts its protein interactions and splicing activities.
- To clarify the role of dephosphorylation in ASF/SF2's function, particularly in activated splicing.
- To elucidate the distinct protein-protein interactions governing constitutive versus activated splicing.
Main Methods:
- Analysis of ASF/SF2 phosphorylation status.
- Assessment of protein-protein interactions with putative targets.
- Functional assays for splicing activation.
Main Results:
- ASF/SF2 phosphorylation differentially affects interactions with various protein targets, showing positive, negative, or no interaction.
- Dephosphorylation of ASF/SF2 is not essential for its role as a splicing activator, unlike its role in constitutive splicing.
- The phosphorylation cycle of ASF/SF2 dynamically modulates its interactions, suggesting context-dependent functions.
Conclusions:
- The phosphorylation state of ASF/SF2 is a key regulator of its interactions with other splicing factors.
- ASF/SF2's function in activated splicing differs from constitutive splicing, particularly regarding the requirement for dephosphorylation.
- Differential protein interactions mediated by ASF/SF2 phosphorylation are critical for distinguishing between constitutive and activated splicing pathways.