An RBPMS-driven splicing regulatory axis including MBNL1, RBFOX2, and QK promotes smooth muscle cell contractile identity.

ABSTRACT: Phenotype switching of vascular smooth muscle cells (SMCs) between contractile and more proliferative and motile states is associated with cardiovascular disease and is underpinned by transcriptional and alternative splicing (AS) programs. We previously showed the RNA-binding protein (RBP) RNA Binding Protein with Multiple Splicing (RBPMS) to be a master regulator of AS in differentiated SMCs. Although changes in master regulator activities can drive AS programs, such proteins rarely act alone. Here we investigated how MBNL1, RBFOX2, and QK act as coregulators with RBPMS to promote contractile smooth muscle AS and phenotypic properties. All four RBPs largely promoted contractile phenotype splicing, with RBPMS showing the highest degree of alignment with the program. Coregulated splicing ev

SUBMITTER: Huang Y 

PROVIDER: S-EPMC12721327 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature