Pre-mRNA splicing is an integral step of eukaryotic gene expression. Splicing its regulation is important for cell survival, proliferation, development, and defects in splicing are associated with many genetic diseases. Although the basic mechanisms of splicing have been well characterized, little is known about how splicing is regulated by cell signaling. SRp38 is a general splicing repressor that is activated by dephosphorylation specifically in mitosis, and in response to heat shock and other cellular stress. This proposed study is to investigate the phosphorylation regulation of SRp38 by the cell cycle and the stress signaling pathways. Results of this study will not only reveal the role of phosphatases in regulating SR protein activity, but also enlighten us as to the general mechanisms by which cell signaling regulates splicing.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM070113-03
Application #
7052040
Study Section
Special Emphasis Panel (ZRG1-F05 (20))
Program Officer
Haynes, Susan R
Project Start
2004-05-01
Project End
2007-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
3
Fiscal Year
2006
Total Cost
$50,428
Indirect Cost
Name
Columbia University (N.Y.)
Department
Biology
Type
Other Domestic Higher Education
DUNS #
049179401
City
New York
State
NY
Country
United States
Zip Code
10027
Shi, Yongsheng; Nishida, Kensei; Campigli Di Giammartino, Dafne et al. (2011) Heat shock-induced SRSF10 dephosphorylation displays thermotolerance mediated by Hsp27. Mol Cell Biol 31:458-65
Shi, Yongsheng; Manley, James L (2007) A complex signaling pathway regulates SRp38 phosphorylation and pre-mRNA splicing in response to heat shock. Mol Cell 28:79-90
Shi, Yongsheng; Reddy, Bharat; Manley, James L (2006) PP1/PP2A phosphatases are required for the second step of Pre-mRNA splicing and target specific snRNP proteins. Mol Cell 23:819-29