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

Stoll, Lisa ; Rodríguez-Trejo, Adriana ; Guay, Claudiane ; Brozzi, Flora ; Bayazit, Mustafa Bilal ; Gattesco, Sonia ; Menoud, Véronique ; Sobel, Jonathan ; Marques, Ana Claudia and Venø, Morten Trillingsgaard , et al. (2020) In Nature Communications 11(1).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
11
issue
1
article number
5611
publisher
Nature Publishing Group
external identifiers
  • scopus:85095425491
  • pmid:33154349
ISSN
2041-1723
DOI
10.1038/s41467-020-19381-w
language
English
LU publication?
yes
id
1005b998-94a6-4a3d-a80a-bd69402aef12
date added to LUP
2020-11-13 08:32:09
date last changed
2024-04-17 19:21:21
@article{1005b998-94a6-4a3d-a80a-bd69402aef12,
  abstract     = {{<p>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.</p>}},
  author       = {{Stoll, Lisa and Rodríguez-Trejo, Adriana and Guay, Claudiane and Brozzi, Flora and Bayazit, Mustafa Bilal and Gattesco, Sonia and Menoud, Véronique and Sobel, Jonathan and Marques, Ana Claudia and Venø, Morten Trillingsgaard and Esguerra, Jonathan Lou S. and Barghouth, Mohammad and Suleiman, Mara and Marselli, Lorella and Kjems, Jørgen and Eliasson, Lena and Renström, Erik and Bouzakri, Karim and Pinget, Michel and Marchetti, Piero and Regazzi, Romano}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{A circular RNA generated from an intron of the insulin gene controls insulin secretion}},
  url          = {{http://dx.doi.org/10.1038/s41467-020-19381-w}},
  doi          = {{10.1038/s41467-020-19381-w}},
  volume       = {{11}},
  year         = {{2020}},
}