A circular RNA generated from an intron of the insulin gene controls insulin secretion.
- Stoll L Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.
- Rodríguez-Trejo A Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.
- Guay C Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.
- Brozzi F Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.
- Bayazit MB Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.
- Gattesco S Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.
- Menoud V Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.
- Sobel J Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.
- Marques AC Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
- Venø MT Interdisciplinary Nanoscience Center (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
- Esguerra JLS Islet Cell Exocytosis or Islet Pathophysiology Group, Lund University Diabetes Centre, Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden.
- Barghouth M Islet Cell Exocytosis or Islet Pathophysiology Group, Lund University Diabetes Centre, Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden.
- Suleiman M Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
- Marselli L Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
- Kjems J Interdisciplinary Nanoscience Center (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
- Eliasson L Islet Cell Exocytosis or Islet Pathophysiology Group, Lund University Diabetes Centre, Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden.
- Renström E Islet Cell Exocytosis or Islet Pathophysiology Group, Lund University Diabetes Centre, Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden.
- Bouzakri K UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France.
- Pinget M UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France.
- Marchetti P Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
- Regazzi R Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland. Romano.Regazzi@unil.ch.
- 2020-11-06
Published in:
- Nature communications. - 2020
Animals
Calcium Signaling
Cell Nucleus
DNA-Binding Proteins
Diabetes Mellitus, Type 2
Gene Expression Regulation
Humans
Insulin
Insulin Secretion
Insulin-Secreting Cells
Introns
Mice
RNA, Circular
Rats
English
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.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1038/s41467-020-19381-w
- PMID 33154349
- Persistent URL
- https://sonar.ch/global/documents/1066
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