N6-methyladenine RNA Methylation Epigenetic Modification and Diabetic Microvascular Complications

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2024 Sep 19

PMID 39296713

Authors

Yuanyuan Wang

Jiayun Zou

Hua Zhou

Affiliations

Soon will be listed here.

Abstract

N6-methyladensine (mA) has been identified as the best-characterized and the most abundant mRNA modification in eukaryotes. It can be dynamically regulated, removed, and recognized by its specific cellular components (respectively called "writers," "erasers," "readers") and have become a hot research field in a variety of biological processes and diseases. Currently, the underlying molecular mechanisms of mA epigenetic modification in diabetes mellitus (DM) and diabetic microvascular complications have not been extensively clarified. In this review, we focus on the effects and possible mechanisms of mA as possible potential biomarkers and therapeutic targets in the treatment of DM and diabetic microvascular complications.

Citing Articles

RNA Modification in Metabolism.

Liu Y, Sun Z, Gui D, Zhao Y, Xu Y MedComm (2020). 2025; 6(3):e70135.

PMID: 40066222 PMC: 11892166. DOI: 10.1002/mco2.70135.

Exploring the methyl-verse: Dynamic interplay of epigenome and m6A epitranscriptome.

Pilala K, Panoutsopoulou K, Papadimitriou M, Soureas K, Scorilas A, Avgeris M Mol Ther. 2024; 33(2):447-464.

PMID: 39659016 PMC: 11852398. DOI: 10.1016/j.ymthe.2024.12.003.

References

Du H, Zhao Y, He J, Zhang Y, Xi H, Liu M . YTHDF2 destabilizes m(6)A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex. Nat Commun. 2016; 7:12626. PMC: 5007331. DOI: 10.1038/ncomms12626. View

Zhang W, Zhang S, Dong C, Guo S, Jia W, Jiang Y . A bibliometric analysis of RNA methylation in diabetes mellitus and its complications from 2002 to 2022. Front Endocrinol (Lausanne). 2022; 13:997034. PMC: 9492860. DOI: 10.3389/fendo.2022.997034. View

De Jesus D, Zhang Z, Kahraman S, Brown N, Chen M, Hu J . mA mRNA Methylation Regulates Human β-Cell Biology in Physiological States and in Type 2 Diabetes. Nat Metab. 2019; 1(8):765-774. PMC: 6924515. DOI: 10.1038/s42255-019-0089-9. View

Yang K, Sun J, Zhang Z, Xiao M, Ren D, Liu S . Reduction of mRNA mA associates with glucose metabolism via YTHDC1 in human and mice. Diabetes Res Clin Pract. 2023; 198:110607. DOI: 10.1016/j.diabres.2023.110607. View

Elafros M, Andersen H, Bennett D, Savelieff M, Viswanathan V, Callaghan B . Towards prevention of diabetic peripheral neuropathy: clinical presentation, pathogenesis, and new treatments. Lancet Neurol. 2022; 21(10):922-936. PMC: 10112836. DOI: 10.1016/S1474-4422(22)00188-0. View

Li X, Jiang Y, Sun X, Wu Y, Chen Z . METTL3 is required for maintaining β-cell function. Metabolism. 2021; 116:154702. DOI: 10.1016/j.metabol.2021.154702. View

Taneera J, Khalique A, Abdrabh S, Mohammed A, Bouzid A, El-Huneidi W . Fat mass and obesity-associated (FTO) gene is essential for insulin secretion and β-cell function: In vitro studies using INS-1 cells and human pancreatic islets. Life Sci. 2024; 339:122421. DOI: 10.1016/j.lfs.2024.122421. View

Leslie R, Ma R, Franks P, Nadeau K, Pearson E, Redondo M . Understanding diabetes heterogeneity: key steps towards precision medicine in diabetes. Lancet Diabetes Endocrinol. 2023; 11(11):848-860. DOI: 10.1016/S2213-8587(23)00159-6. View

Yuan D, Li H, Dai W, Zhou X, Zhou W, He L . IGF2BP3-stabilized CAMK1 regulates the mitochondrial dynamics of renal tubule to alleviate diabetic nephropathy. Biochim Biophys Acta Mol Basis Dis. 2024; 1870(3):167022. DOI: 10.1016/j.bbadis.2024.167022. View

10.

Liu B, Tu Y, Ni G, Yan J, Yue L, Li Z . Total Flavones of Ameliorates Podocyte Pyroptosis and Injury in High Glucose Conditions by Targeting METTL3-Dependent mA Modification-Mediated NLRP3-Inflammasome Activation and PTEN/PI3K/Akt Signaling. Front Pharmacol. 2021; 12:667644. PMC: 8319635. DOI: 10.3389/fphar.2021.667644. View

11.

Jiang A, Song A, Zhang C . Modes of podocyte death in diabetic kidney disease: an update. J Nephrol. 2022; 35(6):1571-1584. DOI: 10.1007/s40620-022-01269-1. View

12.

Zhang L, Qi Y, Aluo Z, Liu S, Zhang Z, Zhou L . Betaine increases mitochondrial content and improves hepatic lipid metabolism. Food Funct. 2018; 10(1):216-223. DOI: 10.1039/c8fo02004c. View

13.

Li Y, Li L, Liu Y, Hu L, Yan Y . Identification of Metabolism-Related Proteins as Biomarkers of Insulin Resistance and Potential Mechanisms of mA Modification. Nutrients. 2023; 15(8). PMC: 10146912. DOI: 10.3390/nu15081839. View

14.

Scuteri A, Sanna S, Chen W, Uda M, Albai G, Strait J . Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet. 2007; 3(7):e115. PMC: 1934391. DOI: 10.1371/journal.pgen.0030115. View

15.

Li C, Su F, Liang Z, Zhang L, Liu F, Fan W . Macrophage M1 regulatory diabetic nephropathy is mediated by m6A methylation modification of lncRNA expression. Mol Immunol. 2022; 144:16-25. DOI: 10.1016/j.molimm.2022.02.008. View

16.

Xu Z, Lv B, Qin Y, Zhang B . Emerging Roles and Mechanism of m6A Methylation in Cardiometabolic Diseases. Cells. 2022; 11(7). PMC: 8997388. DOI: 10.3390/cells11071101. View

17.

Park D, Lee J, Kim J, Kim K, Hong S, Han S . Plastic roles of pericytes in the blood-retinal barrier. Nat Commun. 2017; 8:15296. PMC: 5440855. DOI: 10.1038/ncomms15296. View

18.

Li X, Yang Y, Chen Z . Downregulation of the mA reader protein YTHDC1 leads to islet β-cell failure and diabetes. Metabolism. 2022; 138:155339. DOI: 10.1016/j.metabol.2022.155339. View

19.

Li H, Song Y, He Z, Chen X, Wu X, Li X . Meclofenamic Acid Reduces Reactive Oxygen Species Accumulation and Apoptosis, Inhibits Excessive Autophagy, and Protects Hair Cell-Like HEI-OC1 Cells From Cisplatin-Induced Damage. Front Cell Neurosci. 2018; 12:139. PMC: 5974247. DOI: 10.3389/fncel.2018.00139. View

20.

Geula S, Moshitch-Moshkovitz S, Dominissini D, AlFatah Mansour A, Kol N, Salmon-Divon M . Stem cells. m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation. Science. 2015; 347(6225):1002-6. DOI: 10.1126/science.1261417. View