RNA Methylation in Vascular Disease: a Systematic Review

Overview

Journal J Cardiothorac Surg

Publisher Biomed Central

Specialties Cardiology & Vascular Diseases
General Surgery
Pulmonary Medicine

Date 2022 Dec 19

PMID 36536469

Authors

Yue Shu

Yilong Guo

Yin Zheng

Shuwu He

Zhensu Shi

Affiliations

Soon will be listed here.

Abstract

Despite the rise in morbidity and mortality associated with vascular diseases, the underlying pathophysiological molecular mechanisms are still unclear. RNA N6-methyladenosine modification, as the most common cellular mechanism of RNA regulation, participates in a variety of biological functions and plays an important role in epigenetics. A large amount of evidence shows that RNA N6-methyladenosine modifications play a key role in the morbidity caused by vascular diseases. Further research on the relationship between RNA N6-methyladenosine modifications and vascular diseases is necessary to understand disease mechanisms at the gene level and to provide new tools for diagnosis and treatment. In this study, we summarize the currently available data on RNA N6-methyladenosine modifications in vascular diseases, addressing four aspects: the cellular regulatory system of N6-methyladenosine methylation, N6-methyladenosine modifications in risk factors for vascular disease, N6-methyladenosine modifications in vascular diseases, and techniques for the detection of N6-methyladenosine-methylated RNA.

Citing Articles

Advances in the detection of biomarkers for ischemic stroke.

Liang Y, Chen J, Chen Y, Tong Y, Li L, Xu Y Front Neurol. 2025; 16:1488726.

PMID: 40066310 PMC: 11891058. DOI: 10.3389/fneur.2025.1488726.

References

Meyer K, Jaffrey S . The dynamic epitranscriptome: N6-methyladenosine and gene expression control. Nat Rev Mol Cell Biol. 2014; 15(5):313-26. PMC: 4393108. DOI: 10.1038/nrm3785. View

Saxena R, Weintraub N, Tang Y . Optimizing cardiac ischemic preconditioning and postconditioning via epitranscriptional regulation. Med Hypotheses. 2019; 135:109451. PMC: 6983341. DOI: 10.1016/j.mehy.2019.109451. View

Small T, Pickering J . Nuclear degradation of Wilms tumor 1-associating protein and survivin splice variant switching underlie IGF-1-mediated survival. J Biol Chem. 2009; 284(37):24684-95. PMC: 2757172. DOI: 10.1074/jbc.M109.034629. View

Wang X, Lu Z, Gomez A, Hon G, Yue Y, Han D . N6-methyladenosine-dependent regulation of messenger RNA stability. Nature. 2013; 505(7481):117-20. PMC: 3877715. DOI: 10.1038/nature12730. View

Wu Q, Yuan X, Han R, Zhang H, Xiu R . Epitranscriptomic mechanisms of N6-methyladenosine methylation regulating mammalian hypertension development by determined spontaneously hypertensive rats pericytes. Epigenomics. 2019; 11(12):1359-1370. DOI: 10.2217/epi-2019-0148. View

Xuan J, Sun W, Lin P, Zhou K, Liu S, Zheng L . RMBase v2.0: deciphering the map of RNA modifications from epitranscriptome sequencing data. Nucleic Acids Res. 2017; 46(D1):D327-D334. PMC: 5753293. DOI: 10.1093/nar/gkx934. View

Ruszkowska A, Ruszkowski M, Dauter Z, Brown J . Structural insights into the RNA methyltransferase domain of METTL16. Sci Rep. 2018; 8(1):5311. PMC: 5871880. DOI: 10.1038/s41598-018-23608-8. 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

Roth G, Forouzanfar M, Moran A, Barber R, Nguyen G, Feigin V . Demographic and epidemiologic drivers of global cardiovascular mortality. N Engl J Med. 2015; 372(14):1333-41. PMC: 4482354. DOI: 10.1056/NEJMoa1406656. View

10.

Hsu P, Zhu Y, Ma H, Guo Y, Shi X, Liu Y . Ythdc2 is an N-methyladenosine binding protein that regulates mammalian spermatogenesis. Cell Res. 2017; 27(9):1115-1127. PMC: 5587856. DOI: 10.1038/cr.2017.99. View

11.

Linder B, Grozhik A, Olarerin-George A, Meydan C, Mason C, Jaffrey S . Single-nucleotide-resolution mapping of m6A and m6Am throughout the transcriptome. Nat Methods. 2015; 12(8):767-72. PMC: 4487409. DOI: 10.1038/nmeth.3453. View

12.

Wang L, Xue Y, Li H, Huo R, Yan Z, Wang J . Wilms' tumour 1-associating protein inhibits endothelial cell angiogenesis by m6A-dependent epigenetic silencing of desmoplakin in brain arteriovenous malformation. J Cell Mol Med. 2020; 24(9):4981-4991. PMC: 7205785. DOI: 10.1111/jcmm.15101. View

13.

Meyer K . DART-seq: an antibody-free method for global mA detection. Nat Methods. 2019; 16(12):1275-1280. PMC: 6884681. DOI: 10.1038/s41592-019-0570-0. View

14.

Zhang Z, Chen L, Zhao Y, Yang C, Roundtree I, Zhang Z . Single-base mapping of mA by an antibody-independent method. Sci Adv. 2019; 5(7):eaax0250. PMC: 6609220. DOI: 10.1126/sciadv.aax0250. View

15.

Li A, Chen Y, Ping X, Yang X, Xiao W, Yang Y . Cytoplasmic mA reader YTHDF3 promotes mRNA translation. Cell Res. 2017; 27(3):444-447. PMC: 5339832. DOI: 10.1038/cr.2017.10. View

16.

Wang P, Doxtader K, Nam Y . Structural Basis for Cooperative Function of Mettl3 and Mettl14 Methyltransferases. Mol Cell. 2016; 63(2):306-317. PMC: 4958592. DOI: 10.1016/j.molcel.2016.05.041. View

17.

Ke S, Alemu E, Mertens C, Gantman E, Fak J, Mele A . A majority of m6A residues are in the last exons, allowing the potential for 3' UTR regulation. Genes Dev. 2015; 29(19):2037-53. PMC: 4604345. DOI: 10.1101/gad.269415.115. View

18.

Frayling T, Timpson N, Weedon M, Zeggini E, Freathy R, Lindgren C . A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007; 316(5826):889-94. PMC: 2646098. DOI: 10.1126/science.1141634. View

19.

Garcia-Campos M, Edelheit S, Toth U, Safra M, Shachar R, Viukov S . Deciphering the "mA Code" via Antibody-Independent Quantitative Profiling. Cell. 2019; 178(3):731-747.e16. DOI: 10.1016/j.cell.2019.06.013. View

20.

Song H, Feng X, Zhang H, Luo Y, Huang J, Lin M . METTL3 and ALKBH5 oppositely regulate mA modification of mRNA, which dictates the fate of hypoxia/reoxygenation-treated cardiomyocytes. Autophagy. 2019; 15(8):1419-1437. PMC: 6613905. DOI: 10.1080/15548627.2019.1586246. View