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

Author

Listed:
  • Lisa Stoll

    (University of Lausanne
    Department of Medicine, Weill Cornell Medicine)

  • 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

    (Aarhus University)

  • Jonathan Lou S. Esguerra

    (Lund University)

  • Mohammad Barghouth

    (Lund University)

  • Mara Suleiman

    (University of Pisa)

  • Lorella Marselli

    (University of Pisa)

  • Jørgen Kjems

    (Aarhus University)

  • Lena Eliasson

    (Lund University)

  • Erik Renström

    (Lund University)

  • Karim Bouzakri

    (UMR DIATHEC, EA 7294, Centre Européen d’Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg)

  • Michel Pinget

    (UMR DIATHEC, EA 7294, Centre Européen d’Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg)

  • Piero Marchetti

    (University of Pisa)

  • Romano Regazzi

    (University of Lausanne
    University of Lausanne)

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.

Suggested Citation

  • Lisa Stoll & Adriana Rodríguez-Trejo & Claudiane Guay & Flora Brozzi & Mustafa Bilal Bayazit & Sonia Gattesco & Véronique Menoud & Jonathan Sobel & Ana Claudia Marques & Morten Trillingsgaard Venø & J, 2020. "A circular RNA generated from an intron of the insulin gene controls insulin secretion," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19381-w
    DOI: 10.1038/s41467-020-19381-w
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    Cited by:

    1. Yue Liu & Yue Yang & Chenying Xu & Jianxing Liu & Jiale Chen & Guoqing Li & Bin Huang & Yi Pan & Yanfeng Zhang & Qiong Wei & Stephen J. Pandol & Fangfang Zhang & Ling Li & Liang Jin, 2023. "Circular RNA circGlis3 protects against islet β-cell dysfunction and apoptosis in obesity," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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