The role of m6A and m6Am RNA modifications in the pathogenesis of diabetes mellitus

Daniel Benak; Stepanka Benakova; Lydie Plecita-Hlavata; Marketa Hlavackova

doi:10.3389/fendo.2023.1223583

The role of m⁶A and m⁶Am RNA modifications in the pathogenesis of diabetes mellitus

Front Endocrinol (Lausanne). 2023 Jul 7:14:1223583. doi: 10.3389/fendo.2023.1223583. eCollection 2023.

Authors

Daniel Benak^{1

2}, Stepanka Benakova^{3

4}, Lydie Plecita-Hlavata³, Marketa Hlavackova¹

Affiliations

¹ Laboratory of Developmental Cardiology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czechia.
² Department of Physiology, Faculty of Science, Charles University, Prague, Czechia.
³ Laboratory of Pancreatic Islet Research, Institute of Physiology of the Czech Academy of Sciences, Prague, Czechia.
⁴ First Faculty of Medicine, Charles University, Prague, Czechia.

Abstract

The rapidly developing research field of epitranscriptomics has recently emerged into the spotlight of researchers due to its vast regulatory effects on gene expression and thereby cellular physiology and pathophysiology. N⁶-methyladenosine (m⁶A) and N⁶,2'-O-dimethyladenosine (m⁶Am) are among the most prevalent and well-characterized modified nucleosides in eukaryotic RNA. Both of these modifications are dynamically regulated by a complex set of epitranscriptomic regulators called writers, readers, and erasers. Altered levels of m⁶A and also several regulatory proteins were already associated with diabetic tissues. This review summarizes the current knowledge and gaps about m⁶A and m⁶Am modifications and their respective regulators in the pathophysiology of diabetes mellitus. It focuses mainly on the more prevalent type 2 diabetes mellitus (T2DM) and its treatment by metformin, the first-line antidiabetic agent. A better understanding of epitranscriptomic modifications in this highly prevalent disease deserves further investigation and might reveal clinically relevant discoveries in the future.

Keywords: RNA; T2DM; diabetes; epigenetics; epitranscriptomics; m6A; m6Am; type 2 diabetes mellitus.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Adenosine / metabolism
Diabetes Mellitus, Type 2* / genetics
Humans
RNA / genetics
RNA / metabolism
RNA Processing, Post-Transcriptional
RNA, Messenger / metabolism

Substances

RNA, Messenger
Adenosine
RNA

Grants and funding

This work was supported by the Charles University Grant Agency (grant number GA UK 243423) to SB; the Czech Science Foundation (grant number 19-04790Y) to MH; the Czech Science Foundation (grant number 22-11439S) to LP-H; and the project National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, ID project No. LX22NPO5104) – Funded by the European Union – Next Generation EU.