RNA Methylations in Cardiovascular Diseases, Molecular Structure, Biological Functions and Regulatory Roles in Cardiovascular Diseases

Abstract

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality in the world. Despite considerable progress in the diagnosis, treatment and prognosis of CVDs, new diagnostic biomarkers and new therapeutic measures are urgently needed to reduce the mortality of CVDs and improve the therapeutic effect. RNA methylations regulate almost all aspects of RNA processing, such as RNA nuclear export, translation, splicing and non-coding RNA processing. In view of the importance of RNA methylations in the pathogenesis of diseases, this work reviews the molecular structures, biological functions of five kinds of RNA methylations (m6A, m5C, m1a, m6am and m7G) and their effects on CVDs, including pulmonary hypertension, hypertension, vascular calcification, cardiac hypertrophy, heart failure. In CVDs, m6A “writers” catalyze the installation of m6A on RNAs, while “erasers” remove these modifications. Finally, the “readers” of m6A further influence the mRNA splicing, nuclear export, translation and degradation. M5C, m1A, m6Am and m7G are new types of RNA methylations, their roles in CVDs need to be further explored. RNA methylations have become a new research hotspot and the roles in CVDs is gradually emerging, the review of the molecular characteristics, biological functions and effects of RNA methylation on CVDs will contribute to the elucidation of the pathological mechanisms of CVDs and the discovery of new diagnostic markers and therapeutic targets of CVDs.

29 m6A-RNA Methylation (Epitranscriptomic) Regulators Are Regulated in 41 Diseases including Atherosclerosis and Tumors Potentially via ROS Regulation – 102 Transcriptomic Dataset Analyses

“…Additionally, for further understanding the m 6 A-RMRs's modulation in cardiovascular diseases, our study of m 6 A-RMRs in atherosclerosis and other three studies of m 6 A-RMRs in cardiovascular disease (CVDs) [ 60 – 62 ] were compared. From Table 4 , METTL14 is upregulated in our study and other two studies; FTO is downregulated in our study and other two studies.…”

N1-Methyladenosine (m1A) Regulation Associated With the Pathogenesis of Abdominal Aortic Aneurysm Through YTHDF3 Modulating Macrophage Polarization

“…Similar to m6A modification, N1-Methyladenosine (m1A) is a typical type of RNA methylation, executing its biological functions through post-transcriptional regulation. Besides its role in tumorigenesis and many other biological processes ( 31 ), characteristic m1A modification and regulation have been reported in the pathophysiology of various cardiovascular diseases (CVDs) ( 17 , 32 , 33 ). Hence, it is of great significance to explore the role of m1A regulation in AAA occurrence and development.…”

“…Secondly, RT-qPCR analysis verified that three of the m1A regulators, named YTHDC1, YTHDF1 and YTHDF3 , were up-regulated in AAAs at mRNA level. YTHDC1, YTHDF1 and YTHDF3 , both containing the YTH (YT521-B homology) domain, belong to the “readers” family of m1A methylation, functioning as methylation recognition enzymes that can read methylation sites and corporate with methylases (proteins of “writers” family) ( 17 ). YTHDC1 may participate in the RNA alternative splicing and affect the export of methylated mRNA from the nucleus to the cytoplasm, acting as the biomarker of prostate cancer and colon adenocarcinoma ( 42 ).…”

“…Based on the existing findings of epigenetic regulation in AAA, we started to focus on other types of RNA methylation modifications in AAA, especially N1-Methyladenosine (m1A) modification. M1A modification changes the secondary structure of RNAs by adding a methyl group to the N1 position of adenosine, thus affecting the interaction between RNAs and proteins ( 17 ). M1A methylation is found in rRNAs, tRNAs, mRNAs and mitochondrial RNAs, regulated by three types of m1A regulators: First, m1A “writers,” including TRMT6 / TRMT61A, TRMT61B, TRMT10C, BMT2 and RRP8 , work as methyltransferases to add m1A modification on RNAs; Second, m1A “erasers,” containing FTO, ALKBH1-3 , can eliminate the modification of m1A; Third, m1A “readers,” comprising YTHDF1-3 and YTHDC1 , serve as RNA binding proteins which can read m1A methylation modification information as well as recognizing and binding to m1A methylation sites ( 17 – 19 ).…”

“…M1A modification changes the secondary structure of RNAs by adding a methyl group to the N1 position of adenosine, thus affecting the interaction between RNAs and proteins ( 17 ). M1A methylation is found in rRNAs, tRNAs, mRNAs and mitochondrial RNAs, regulated by three types of m1A regulators: First, m1A “writers,” including TRMT6 / TRMT61A, TRMT61B, TRMT10C, BMT2 and RRP8 , work as methyltransferases to add m1A modification on RNAs; Second, m1A “erasers,” containing FTO, ALKBH1-3 , can eliminate the modification of m1A; Third, m1A “readers,” comprising YTHDF1-3 and YTHDC1 , serve as RNA binding proteins which can read m1A methylation modification information as well as recognizing and binding to m1A methylation sites ( 17 – 19 ). Although m1A modification patterns have been reported in a variety of diseases, involving Ovarian Cancer, Pancreatic Cancer and Oral Squamous Cell Carcinoma ( 19 – 21 ), there are currently no relevant reports of m1A modification and regulation in AAA, motivating us to perform research on the role of m1A regulation in AAA.…”