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SAM68 is a crucial post-transcriptional regulator of cardiogenesis

ABSTRACT: RNA-binding proteins (RBPs) of the STAR family play important roles in mammalian development, yet their precise contributions to lineage specification remain incompletely understood. Here, using CRISPR–Cas9 knockout models combined with multi-omics approaches, we investigate the roles of two STAR proteins, SAM68 and QKI, in mouse embryonic stem cells (mESCs). Both RBPs contribute to mESC proliferation, self-renewal, and efficient differentiation into cardiomyocytes. Our data support a role for QKI in the regulation of cardiac differentiation programs. In addition, our analyses reveal a previously underappreciated contribution of SAM68 to cardiomyocyte specification, acting through multiple post-transcriptional mechanisms. Despite belonging to the same protein family, SAM68 and QKI regulate largely distinct post-transcriptional programs during differentiation. Specifically, SAM68 modulates alternative splicing and promotes the biogenesis of a subset of cardiac-enriched circular RNAs through binding to intronic regions flanking back-splice sites and association with NF90/110. In addition, SAM68 associates with untranslated regions of key differentiation-related transcripts, including Gata4 mRNA, a key transcription factor regulating cardiogenesis, and likely functions in complex with other RNA-binding proteins to regulate these transcripts. Together, these findings identify SAM68 as a regulator of multiple RNA processing pathways contributing to cardiomyocyte differentiation and provide insight into how STAR proteins shape post-transcriptional gene regulatory networks during early development.

ORGANISM(S): Mus musculus

PROVIDER: GSE326251 | GEO | 2026/04/02

REPOSITORIES: GEO

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Role of the STAR proteins in early mammalian development [RNA-seq]

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