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bioRxiv · 10.1101/759829

SRPK3 regulates alternative pre-mRNA splicing required for B lymphocyte development and humoral responsiveness

Arends, T.·Taliaferro, J. M.·Peterman, E.·Knapp, J. R.·O'Connor, B. P.·Torres, R. M.·Hagman, J. R.
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Abstract

Alternative splicing (AS) of pre-mRNA is a critical component of transcriptional regulation that diversifies the cellular proteome. The Serine-Arginine Protein Kinases (SRPK) initiate early events in AS. Using conditional knockout mice (cKO), we demonstrated the importance of the X-linked gene Srpk3 in B lymphocyte development and in response to immunization in vivo. Significantly decreased numbers of immature and mature B cells were observed in Srpk3-cKO BM relative to wild-type (WT). Immunization of Srpk3-cKO mice with a T lymphocyte-independent type-2 antigen elicited greatly reduced amounts of specific IgG3. Srpk3 deletion resulted in hundreds of differentially spliced mRNAs in B cells, including mRNAs encoding proteins associated with signaling pathways and mitochondrial function. Several alternative splicing outcomes in Srpk3-cKO cells are due to altered splicing regulation of SR proteins. We conclude that Srpk3 is an immunomodulatory kinase that controls humoral immunity via its regulation of pre-mRNA splicing, antibody production, and metabolism in B cells.\n\nOne Sentence SummarySRPK3 regulates alternative splicing of pre-mRNA that is crucial for B cell development, activation and antibody responses.

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Arends, T., Taliaferro, J. M., Peterman, E., Knapp, J. R., O'Connor, B. P., Torres, R. M., Hagman, J. R.. 2019-09-08. SRPK3 regulates alternative pre-mRNA splicing required for B lymphocyte development and humoral responsiveness. https://doi.org/10.1101/759829

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