Human Tra2 proteins jointly control a CHEK1 splicing switch among alternative and constitutive target exons

Best, Andrew, James, Katherine, Dalgliesh, Caroline, Hong, Elaine, Kheirolahi-Kouhestani, Mahsa, Curk, Tomaz, Xu, Yaobo, Danilenko, Marina, Hussain, Rafiq, Keavney, Bernard, Wipat, Anil, Klinck, Roscoe, Cowell, Ian G., Cheong Lee, Ka, Austin, Caroline A., Venables, Julian P., Chabot, Benoit, Santibanez Koref, Mauro, Tyson-Capper, Alison and Elliott, David J. (2014) Human Tra2 proteins jointly control a CHEK1 splicing switch among alternative and constitutive target exons. Nature Communications, 5 (1). ISSN 2041-1723

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Official URL: https://doi.org/10.1038/ncomms5760

Abstract

Alternative splicing—the production of multiple messenger RNA isoforms from a single gene—is regulated in part by RNA binding proteins. While the RBPs transformer2 alpha (Tra2α) and Tra2β have both been implicated in the regulation of alternative splicing, their relative contributions to this process are not well understood. Here we find simultaneous—but not individual—depletion of Tra2α and Tra2β induces substantial shifts in splicing of endogenous Tra2β target exons, and that both constitutive and alternative target exons are under dual Tra2α–Tra2β control. Target exons are enriched in genes associated with chromosome biology including CHEK1, which encodes a key DNA damage response protein. Dual Tra2 protein depletion reduces expression of full-length CHK1 protein, results in the accumulation of the DNA damage marker γH2AX and decreased cell viability. We conclude Tra2 proteins jointly control constitutive and alternative splicing patterns via paralog compensation to control pathways essential to the maintenance of cell viability.

Item Type: Article
Uncontrolled Keywords: Alternative Splicing, Cell Line, Tumor, Exons, Humans, MCF-7 Cells, Nerve Tissue Proteins, metabolism, Protein Kinases, genetics/metabolism, RNA, Messenger, RNA-Binding Proteins
Subjects: C100 Biology
C500 Microbiology
C700 Molecular Biology, Biophysics and Biochemistry
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Rachel Branson
Date Deposited: 28 Feb 2020 10:07
Last Modified: 28 Feb 2020 10:15
URI: http://nrl.northumbria.ac.uk/id/eprint/42275

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