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

Lisa Stoll, Adriana Rodríguez-Trejo, Claudiane Guay, Flora Brozzi, Mustafa Bilal Bayazit, Sonia Gattesco, Véronique Menoud, Jonathan Sobel, Ana Claudia Marques, Morten Trillingsgaard Venø, Jonathan Lou S. Esguerra, Mohammad Barghouth, Mara Suleiman, Lorella Marselli, Jørgen Kjems, Lena Eliasson, Erik Renström, Karim Bouzakri, Michel Pinget, Piero Marchetti and Romano Regazzi ()
Additional contact information
Lisa Stoll: University of Lausanne
Adriana Rodríguez-Trejo: University of Lausanne
Claudiane Guay: University of Lausanne
Flora Brozzi: University of Lausanne
Mustafa Bilal Bayazit: University of Lausanne
Sonia Gattesco: University of Lausanne
Véronique Menoud: University of Lausanne
Jonathan Sobel: University of Lausanne
Ana Claudia Marques: University of Lausanne
Morten Trillingsgaard Venø: Aarhus University
Jonathan Lou S. Esguerra: Lund University
Mohammad Barghouth: Lund University
Mara Suleiman: University of Pisa
Lorella Marselli: University of Pisa
Jørgen Kjems: Aarhus University
Lena Eliasson: Lund University
Erik Renström: Lund University
Karim Bouzakri: UMR DIATHEC, EA 7294, Centre Européen d’Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg
Michel Pinget: UMR DIATHEC, EA 7294, Centre Européen d’Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg
Piero Marchetti: University of Pisa
Romano Regazzi: University of Lausanne

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19381-w

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