Allemand, E., Hastings, M. L., Murray, M. V., Myers, M. P., Krainer, A. R. (July 2007) Alternative splicing regulation by interaction of phosphatase PP2Cgamma with nucleic acid-binding protein YB-1. Nat Struct Mol Biol, 14 (7). pp. 630-638. ISSN 1545-9993 (Print)
Abstract
Kinases and phosphatases participate in precursor messenger RNA (pre-mRNA) splicing regulation, but their precise roles and the identities of their cofactors and substrates remain poorly understood. The human Ser/Thr phosphatase PP2Cgamma promotes spliceosome assembly. We show that PP2Cgamma's distinctive acidic domain is essential for its activity in splicing and interacts with YB-1, a spliceosome-associated factor. Moreover, PP2Cgamma is a phosphoprotein in vivo, and its acidic domain is phosphorylated under splicing conditions in vitro. PP2Cgamma phosphorylation enhances its interaction with YB-1 and is reversed by the phosphatase in cis. PP2Cgamma knockdown leaves constitutive splicing unaffected but inhibits cell proliferation and affects alternative splicing of CD44, a YB-1 target. This effect on splicing regulation is mediated by PP2Cgamma's acidic domain, which is essential to promote inclusion of CD44 exons v4 and v5 in vivo. We propose that PP2Cgamma modulates alternative splicing of specific pre-mRNAs coregulated by YB-1.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Alternative Splicing bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > pre-mRNA bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > protein phosphatase |
| CSHL Authors: | |
| Communities: | CSHL labs > Krainer lab |
| Depositing User: | CSHL Librarian |
| Date: | July 2007 |
| Date Deposited: | 02 Dec 2011 15:28 |
| Last Modified: | 09 Apr 2014 14:16 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/22957 |
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