Cyclin-dependent kinase 1 (CDK1) and CDK2 have opposing roles in regulating interactions of splicing factor 3B1 with chromatin

The Journal of Biological Chemistry
Tushar MurthyAlex C Minella

Abstract

Splicing factor 3B1 (SF3B1) is a core splicing protein that stabilizes the interaction between the U2 snRNA and the branch point in the mRNA target during splicing. SF3B1 is heavily phosphorylated at its N terminus and a substrate of cyclin-dependent kinases (CDKs). Although SF3B1 phosphorylation coincides with splicing catalysis, the functional significance of SF3B1 phosphorylation is largely undefined. Here, we show that SF3B1 phosphorylation follows a dynamic pattern during cell cycle progression that depends on CDK activity. SF3B1 is known to interact with chromatin, and we found that SF3B1 maximally interacts with nucleosomes during G1/S and that this interaction requires CDK2 activity. In contrast, SF3B1 disassociates from nucleosomes at G2/M, coinciding with a peak in CDK1-mediated SF3B1 phosphorylation. Thus, CDK1 and CDK2 appear to have opposing roles in regulating SF3B1-nucleosome interactions. Importantly, these interactions were modified by the presence and phosphorylation status of linker histone H1, particularly the H1.4 isoform. Performing genome-wide analysis of SF3B1-chromatin binding in synchronized cells, we observed that SF3B1 preferentially bound exons. Differences in SF3B1 chromatin binding to specific sit...Continue Reading

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Citations

May 31, 2019·Nucleic Acids Research·Joana Carlevaro-FitaJianwei Li
Sep 20, 2018·F1000Research·Kirsten A Reimer, Karla M Neugebauer
Sep 21, 2020·Trends in Genetics : TIG·Mayra PetasnyMaayan Salton
May 31, 2021·Trends in Cell Biology·Chen ChuPiotr Sicinski

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