Glucose Regulates m6A Methylation of RNA in Pancreatic Islets

被引：25

作者：

Bornaque, Florine ^{[1
]}

Delannoy, Clement Philippe ^{[1
]}

Courty, Emilie ^{[1
]}

Rabhi, Nabil ^{[1
,3
]}

Carney, Charlene ^{[1
]}

Rolland, Laure ^{[1
]}

Moreno, Maeva ^{[1
]}

Gromada, Xavier ^{[1
]}

Bourouh, Cyril ^{[1
]}

Petit, Pauline ^{[2
]}

Durand, Emmanuelle ^{[1
]}

Pattou, Francois ^{[2
]}

Kerr-Conte, Julie ^{[2
]}

Froguel, Philippe ^{[1
]}

Bonnefond, Amelie ^{[1
]}

Oger, Frederik ^{[1
]}

Annicotte, Jean-Sebastien ^{[1
]}

机构：

[1] Univ Lille, CHU Lille, Inst Pasteur Lille, EGID,INSERM,CNRS,U1283,UMR 8199, F-59000 Lille, France

[2] Univ Lille, CHU Lille, INSERM, EGID,U1190, F-59000 Lille, France

[3] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA

来源：

CELLS | 2022年 / 11卷 / 02期

关键词：

epitranscriptome; insulin secretion; pancreatic beta cell; type; 2; diabetes; BETA-CELL DYSFUNCTION; MESSENGER-RNA; NUCLEAR-RNA; GENE-EXPRESSION; FTO; N-6-METHYLADENOSINE; PROGRESSION; N6-METHYLADENOSINE; TRANSLATION; FAILURE;

D O I：

10.3390/cells11020291

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Type 2 diabetes is characterized by chronic hyperglycemia associated with impaired insulin action and secretion. Although the heritability of type 2 diabetes is high, the environment, including blood components, could play a major role in the development of the disease. Amongst environmental effects, epitranscriptomic modifications have been recently shown to affect gene expression and glucose homeostasis. The epitranscriptome is characterized by reversible chemical changes in RNA, with one of the most prevalent being the m(6)A methylation of RNA. Since pancreatic beta cells fine tune glucose levels and play a major role in type 2 diabetes physiopathology, we hypothesized that the environment, through variations in blood glucose or blood free fatty acid concentrations, could induce changes in m(6)A methylation of RNAs in pancreatic beta cells. Here we observe a significant decrease in m(6)A methylation upon high glucose concentration, both in mice and human islets, associated with altered expression levels of m(6)A demethylases. In addition, the use of siRNA and/or specific inhibitors against selected m(6)A enzymes demonstrate that these enzymes modulate the expression of genes involved in pancreatic beta-cell identity and glucose-stimulated insulin secretion. Our data suggest that environmental variations, such as glucose, control m(6)A methylation in pancreatic beta cells, playing a key role in the control of gene expression and pancreatic beta-cell functions. Our results highlight novel causes and new mechanisms potentially involved in type 2 diabetes physiopathology and may contribute to a better understanding of the etiology of this disease.

引用

页数：20

共 57 条

[1] Epigenetic modifications and long noncoding RNAs influence pancreas development and function [J].