A role for alternative splicing in circadian control of exocytosis and glucose homeostasis.

ABSTRACT: The circadian clock is encoded by a negative transcriptional feedback loop that coordinates physiology and behavior through molecular programs that remain incompletely understood. Here, we reveal rhythmic genome-wide alternative splicing (AS) of pre-mRNAs encoding regulators of peptidergic secretion within pancreatic β cells that are perturbed in Clock^-/- and Bmal1^-/- β-cell lines. We show that the RNA-binding protein THRAP3 (thyroid hormone receptor-associated protein 3) regulates circadian clock-dependent AS by binding to exons at coding sequences flanking exons that are more frequently skipped in clock mutant β cells, including transcripts encoding Cask (calcium/calmodulin-dependent serine protein kinase) and Madd (MAP kinase-a

SUBMITTER: Marcheva B 

PROVIDER: S-EPMC7397853 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature