A circular RNA generated from an intron of the insulin gene controls insulin secretion.

ABSTRACT: Fine-tuning of insulin release from pancreatic ?-cells is essential to maintain blood glucose homeostasis. Here, we report that insulin secretion is regulated by a circular RNA containing the lariat sequence of the second intron of the insulin gene. Silencing of this intronic circular RNA in pancreatic islets leads to a decrease in the expression of key components of the secretory machinery of ?-cells, resulting in impaired glucose- or KCl-induced insulin release and calcium signaling. The effect of the circular RNA is exerted at the transcriptional level and involves an interaction with the RNA-binding protein TAR DNA-binding protein 43?kDa (TDP-43). The level of this circularized intron is reduced in the islets of rodent diabetes models and of type 2 diabetic patients, possibly explaining their impaired secretory capacity. The study of this and other circular RNAs helps understanding ?-cell dysfunction under diabetes conditions, and the etiology of this common metabolic disorder.

SUBMITTER: Stoll L 

PROVIDER: S-EPMC7644714 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature