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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Lisa Stoll
  • Adriana Rodríguez-Trejo
  • Claudiane Guay
  • Flora Brozzi
  • Mustafa Bilal Bayazit
  • Sonia Gattesco
  • Véronique Menoud
  • Jonathan Sobel
  • Ana Claudia Marques
  • Morten Trillingsgaard Venø
  • Mara Suleiman
  • Lorella Marselli
  • Jørgen Kjems
  • Karim Bouzakri
  • Michel Pinget
  • Piero Marchetti
  • Romano Regazzi
Organisations
External organisations
  • University of Lausanne
  • Aarhus University
  • University of Pisa
  • University of Strasbourg
  • Cornell University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Article number5611
JournalNature Communications
Volume11
Issue number1
Publication statusPublished - 2020
Publication categoryResearch
Peer-reviewedYes