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

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  • 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
  • ,
  • Jonathan Lou S. Esguerra, Lund University
  • ,
  • Mohammad Barghouth, Lund University
  • ,
  • Mara Suleiman, University of Pisa
  • ,
  • Lorella Marselli, University of Pisa
  • ,
  • Jørgen Kjems
  • Lena Eliasson, Lund University
  • ,
  • Erik Renström, Lund University
  • ,
  • Karim Bouzakri, Université de Strasbourg
  • ,
  • Michel Pinget, Université de Strasbourg
  • ,
  • Piero Marchetti, University of Pisa
  • ,
  • Romano Regazzi, University of Lausanne

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.

Original languageEnglish
Article number5611
JournalNature Communications
Volume11
ISSN2041-1723
DOIs
Publication statusPublished - Nov 2020

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