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

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

doi:10.1038/s41467-020-19381-w

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

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

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

60 Citations (Scopus)

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.

Original language	English
Article number	5611
Journal	Nature Communications
Volume	11
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-020-19381-w
Publication status	Published - Nov 2020

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Stoll, L., Rodríguez-Trejo, A., Guay, C., Brozzi, F., Bayazit, M. B., Gattesco, S., Menoud, V., Sobel, J., Marques, A. C., Venø, M. T., Esguerra, J. L. S., Barghouth, M., Suleiman, M., Marselli, L., Kjems, J., Eliasson, L., Renström, E., Bouzakri, K., Pinget, M., ... Regazzi, R. (2020). A circular RNA generated from an intron of the insulin gene controls insulin secretion. Nature Communications, 11, Article 5611. https://doi.org/10.1038/s41467-020-19381-w

@article{69fca71970974ef8953497a314453e66,

title = "A circular RNA generated from an intron of the insulin gene controls insulin secretion",

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.",

author = "Lisa Stoll and Adriana Rodr{\'i}guez-Trejo and Claudiane Guay and Flora Brozzi and Bayazit, {Mustafa Bilal} and Sonia Gattesco and V{\'e}ronique Menoud and Jonathan Sobel and Marques, {Ana Claudia} and Ven{\o}, {Morten Trillingsgaard} and Esguerra, {Jonathan Lou S.} and Mohammad Barghouth and Mara Suleiman and Lorella Marselli and J{\o}rgen Kjems and Lena Eliasson and Erik Renstr{\"o}m and Karim Bouzakri and Michel Pinget and Piero Marchetti and Romano Regazzi",

year = "2020",

month = nov,

doi = "10.1038/s41467-020-19381-w",

language = "English",

volume = "11",

journal = "Nature Communications",

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publisher = "Nature Research",

}

Stoll, L, Rodríguez-Trejo, A, Guay, C, Brozzi, F, Bayazit, MB, Gattesco, S, Menoud, V, Sobel, J, Marques, AC, Venø, MT, Esguerra, JLS, Barghouth, M, Suleiman, M, Marselli, L, Kjems, J, Eliasson, L, Renström, E, Bouzakri, K, Pinget, M, Marchetti, P & Regazzi, R 2020, 'A circular RNA generated from an intron of the insulin gene controls insulin secretion', Nature Communications, vol. 11, 5611. https://doi.org/10.1038/s41467-020-19381-w

TY - JOUR

T1 - A circular RNA generated from an intron of the insulin gene controls insulin secretion

AU - Stoll, Lisa

AU - Rodríguez-Trejo, Adriana

AU - Guay, Claudiane

AU - Brozzi, Flora

AU - Bayazit, Mustafa Bilal

AU - Gattesco, Sonia

AU - Menoud, Véronique

AU - Sobel, Jonathan

AU - Marques, Ana Claudia

AU - Venø, Morten Trillingsgaard

AU - Esguerra, Jonathan Lou S.

AU - Barghouth, Mohammad

AU - Suleiman, Mara

AU - Marselli, Lorella

AU - Kjems, Jørgen

AU - Eliasson, Lena

AU - Renström, Erik

AU - Bouzakri, Karim

AU - Pinget, Michel

AU - Marchetti, Piero

AU - Regazzi, Romano

PY - 2020/11

Y1 - 2020/11

N2 - 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.

AB - 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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DO - 10.1038/s41467-020-19381-w

M3 - Journal article

C2 - 33154349

AN - SCOPUS:85095425491

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

M1 - 5611

ER -

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

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