Decoding SR protein regulation: kinases, phosphatases, and therapeutic targeting strategies

TL;DR

This review explores how SR proteins, which are important for RNA splicing, are regulated by phosphorylation and how targeting this process could lead to new cancer treatments.

Contribution

The paper provides a comprehensive overview of kinase and phosphatase networks regulating SR proteins and their therapeutic implications in cancer.

Findings

SR proteins are regulated by phosphorylation and dephosphorylation, which are critical for their function in RNA splicing.

Targeting SR protein phosphorylation could offer new therapeutic strategies for cancer treatment.

Combining SR protein-targeting drugs with other therapies may enhance cancer treatment efficacy.

Abstract

RNA splicing is a fundamental cellular process that transforms precursor messenger RNA (pre-mRNA) into mature messenger RNA (mRNA) by removing non-coding introns and rejoining coding exons. Serine/arginine-rich (SR) proteins, a family of RNA-binding proteins, play crucial roles in RNA splicing by recruiting essential components for spliceosome assembly. The activity of SR proteins is tightly regulated by post-translational modifications, including phosphorylation, acetylation, methylation, and ubiquitination. Among these, the dynamic balance between phosphorylation and dephosphorylation is particularly critical for modulating SR protein function. Given their involvement in cancer, SR proteins represent promising targets for therapeutic intervention. In this review, we provide a comprehensive overview of the current understanding of the regulatory networks involving kinases and phosphatases governing SR protein phosphorylation. We also discuss the existing therapeutic strategies using small-molecule inhibitors aimed at regulating SR protein phosphorylation in the context of cancer. In conclusion, this review highlights the importance of phosphorylation regulation in SR protein function and the RNA splicing process. Targeting SR protein phosphorylation may open new therapeutic avenues or enhance the efficacy of cancer treatments when used in combination with other drugs.

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