A circular RNA generated from an intron of the insulin gene controls insulin secretion. Academic Article uri icon

Overview

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.

authors

  • Stoll, Lisa
  • Rodríguez-Trejo, Adriana
  • Guay, Claudiane
  • Brozzi, Flora
  • Bayazit, Mustafa Bilal
  • Gattesco, Sonia
  • Menoud, Véronique
  • Sobel, Jonathan
  • Marques, Ana Claudia
  • Venø, Morten Trillingsgaard
  • Esguerra, Jonathan Lou S
  • Barghouth, Mohammad
  • Suleiman, Mara
  • Marselli, Lorella
  • Kjems, Jørgen
  • Eliasson, Lena
  • Renström, Erik
  • Bouzakri, Karim
  • Pinget, Michel
  • Marchetti, Piero
  • Regazzi, Romano

publication date

  • November 5, 2020

Research

keywords

  • Insulin
  • Insulin Secretion
  • Introns
  • RNA, Circular

Identity

PubMed Central ID

  • PMC7644714

Scopus Document Identifier

  • 85095425491

Digital Object Identifier (DOI)

  • 10.1093/nar/gkw377

PubMed ID

  • 33154349

Additional Document Info

volume

  • 11

issue

  • 1