RNA-binding protein Cpeb1 is a marker of healthy adult ß cells in mice but is dispensable ß cell identity and function
RNA binding proteins (RBPs) are increasingly being recognized as important regulators of pancreatic ß-cells' identity and function. We identified the poly-A binding RBP, Cpeb1, as a potential new regulator linked to ß-cell failure in diabetes based on its enrichment in mature, healthy adult ß-cells and its sharp decrease in ß-cells in type 1 diabetes (T1D) and type 2 diabetes (T2D). While Cpeb1 is known to regulate an extensive range of biological processes and its involvement in regulating genes involved in insulin signaling and apoptosis in the liver has been reported, Cpeb1 function in ß-cells is unknown. Here, we have used two independent genetic models, namely ß-cell-specific and whole body Cpeb1 deletions, to assess the role of Cpeb1 in ß-cells. We show Cpeb1 function is dispensable for ß-cell function and identity. Using bulk RNA sequencing on islets of both models, we also show that Cpeb1 regulates markedly different sets of genes between male and female islets, both at the transcriptional and at the polyadenylation levels. Overall design: RNA-seq profiling of ß cell-specific Cpeb1 knockout primary islets (Cpeb1 ßKO: Cpeb1flx/flx; Ins1-Cre) and wildtype control (Cpeb1+/+; Ins1-Cre), and of whole-body knockout of Cpeb1 islets (Cpeb1 KO) and wildtype control.