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Alternative Splicing of a Novel Inducible Exon Diversifies the CASK Guanylate Kinase Domain

Dembowski, Jill A. and An, Ping and Scoulos-Hanson, Maritsa and Yeo, Gene and Han, Joonhee and Fu, Xiang-Dong and Grabowski, Paula J. (2012) Alternative Splicing of a Novel Inducible Exon Diversifies the CASK Guanylate Kinase Domain. Journal of Nucleic Acids, 2012. pp. 1-15. ISSN 2090-0201

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Alternative pre-mRNA splicing has a major impact on cellular functions and development with the potential to fine-tune cellular localization, posttranslational modification, interaction properties, and expression levels of cognate proteins. The plasticity of regulation sets the stage for cells to adjust the relative levels of spliced mRNA isoforms in response to stress or stimulation. As part of an exon profiling analysis of mouse cortical neurons stimulated with high KCl to induce membrane depolarization, we detected a previously unrecognized exon (E24a) of the CASK gene, which encodes for a conserved peptide insertion in the guanylate kinase interaction domain. Comparative sequence analysis shows that E24a appeared selectively in mammalian CASK genes as part of a >3,000 base pair intron insertion. We demonstrate that a combination of a naturally defective
5 splice site and negative regulation by several splicing factors, including SC35 (SRSF2) and ASF/SF2 (SRSF1), drives E24a skipping in most cell types. However, this negative regulation is countered with an observed increase in E24a inclusion after neuronal stimulation and NMDA receptor signaling. Taken together, E24a is typically a skipped exon, which awakens during neuronal stimulation with the potential to diversify the protein interaction properties of the CASK polypeptide.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Dembowski, Jill A.
Scoulos-Hanson, Maritsa
Yeo, Gene
Han, Joonhee
Fu, Xiang-Dong
Grabowski, Paula
Date: 2012
Date Type: Publication
Journal or Publication Title: Journal of Nucleic Acids
Volume: 2012
Publisher: Hindawi Limited
Page Range: pp. 1-15
DOI or Unique Handle: 10.1155/2012/816237
Schools and Programs: Dietrich School of Arts and Sciences > Biological Sciences
Refereed: Yes
ISSN: 2090-0201
Official URL:
Article Type: Research Article
Date Deposited: 30 Apr 2020 00:08
Last Modified: 30 Apr 2020 00:08


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