Tent5a polyadenylation of insulin mRNA regulates pancreatic beta cells
Tent5a was identified as a positive regulator of insulin production in pancreatic beta cells. Overexpression extended poly(A) tails of insulin transcripts and increased insulin content.
Tent5a is a positive regulator of insulin production in pancreatic beta cells, according to a functional RNAi screen of RNA binding proteins. Increased Tent5a expression positively correlates with obese and normoglycemic mouse models exhibiting compensated beta cell function, while its levels negatively correlate with beta cell failure.
Pancreatic beta cells can compensate for increased metabolic demand by increasing their function, but less is known how beta cells increase insulin synthesis and secretion. Increased Tent5a expression can be triggered by ribosome collisions and is repressed by ER stress and lipotoxic inflammation.
Tent5a overexpression extended the poly(A) tails of insulin transcripts, enhanced mRNA stability and increased insulin content in INS-1E cells and human islets microtissues, while Tent5a knockout cells showed shortened insulin mRNA half-life and reduced insulin content. Cytosolic polyadenylation activity is dependent on Tent5a tethering to the endoplasmic reticulum via Fndc3 proteins, leading to increased ER function.
The data identify a role of Tent5a in enhancing insulin production, which may be involved in boosting insulin synthesis and maintaining euglycemia in obesity.