A role for alternative splicing in circadian control of insulin secretion and glucose homeostasis

We report the discovery of circadian clock-controlled alterantive pre-mRNA splicing in pancreatic beta cells and its role in insulin secretion. We performed RNA-sequencing in CRISPR-CAS9 edited Clock and Bmal1 knockout BetaTC6 cells and used differential mRNA expression and splicing analysis to identify and validate transcriptional and alternative splicing targets of the circadian clock regulating insulin secretion. We have profiled the transcriptomes of wild type and Bmal1 knockout pancreatic beta cells by RNA-seq and performed ChIP-seq and eCLIP-seq to map the DNA and RNA binding positions of the RNA binding protein THRAP3 in these cells.