Fine-tuning of insulin release from pancreatic β-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 β-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 β-cell dysfunction under diabetes conditions, and the etiology of this common metabolic disorder.

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

Suleiman M.;Marselli L.;Marchetti P.;
2020-01-01

Abstract

Fine-tuning of insulin release from pancreatic β-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 β-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 β-cell dysfunction under diabetes conditions, and the etiology of this common metabolic disorder.
2020
Stoll, L.; Rodriguez-Trejo, A.; Guay, C.; Brozzi, F.; Bayazit, M. B.; Gattesco, S.; Menoud, V.; Sobel, J.; Marques, A. C.; Veno, M. T.; Esguerra, J. L. S.; Barghouth, M.; Suleiman, M.; Marselli, L.; Kjems, J.; Eliasson, L.; Renstrom, E.; Bouzakri, K.; Pinget, M.; Marchetti, P.; Regazzi, R.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1076135
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