Role of m6A RNA methylation in cardiovascular disease (Review)

Abstract

N 6 -methyladenosine (m 6 A) is the most prevalent and abundant type of internal post-transcriptional RNA modification in eukaryotic cells. Multiple types of RNA, including mRNAs, rRNAs, tRNAs, long non-coding RNAs and microRNAs, are involved in m 6 A methylation. The biological function of m 6 A modification is dynamically and reversibly mediated by methyltransferases (writers), demethylases (erasers) and m 6 A binding proteins (readers). The methyltransferase complex is responsible for the catalyzation of m 6 A modification and is typically made up of methyltransferase-like (METTL)3, METTL14 and Wilms tumor 1-associated protein. Erasers remove methylation by fat mass and obesity-associated protein and ALKB homolog 5. Readers play a role through the recognition of m 6 A-modified targeted RNA. The YT521-B homology domain family, heterogeneous nuclear ribonucleoprotein and insulin-like growth factor 2 mRNA-binding protein serve as m 6 A readers. The m 6 A methylation on transcripts plays a pivotal role in the regulation of downstream molecular events and biological functions, such as RNA splicing, transport, stability and translatability at the post-transcriptional level. The dysregulation of m 6 A modification is associated with cancer, drug resistance, virus replication and the pluripotency of embryonic stem cells. Recently, a number of studies have identified aberrant m 6 A methylation in cardiovascular diseases (CVDs), including cardiac hypertrophy, heart failure, arterial aneurysm, vascular calcification and pulmonary hypertension. The aim of the present review article was to summarize the recent research progress on the role of m 6 A modification in CVD and give a brief perspective on its prospective applications in CVD.

Transcriptome-Wide High-Throughput m6A Sequencing of Differential m6A Methylation Patterns in the Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes Cell Line MH7A

“…5 This means that the m6A methylation modification is a dynamic reversible process. 6 Various m6A methyltransferases, known as “writers,” including methyltransferase-like 3 (METTL3), METTL14 and Wilms tumor 1-associated protein (WTAP), catalyze the m6A methylation of mRNA. 5 , 7 Various m6A demethylases are called “erasers”, including fat mass and obesity-associated protein (FTO) and ALKB family member 5 (ALKBH5), which function is to reduce the modified RNA to the original RNA.…”

Potential role of m6A RNA methylation regulators in osteosarcoma and its clinical prognostic value

“…In addition, non-coding RNAs such as long noncoding RNA and miRNA also have m6A modification sites. M6A modification on mRNA, similar to DNA and protein modification, can be reversibly and dynamically regulated by methyltransferases (writers), m6A-binding proteins (readers), and demethylases (erasers) [ 6 ]. Methyltransferase is an important class of catalytic enzymes, which can cause the m6A methylation in mRNA, mainly including METTL3, METTL14, METTL16, WTAP, VIRMA, RBM15, and ZC3H13 [ 7 – 10 ].…”

Epitranscriptomics of Ischemic Heart Disease—The IHD-EPITRAN Study Design and Objectives

“…Although the study of RNA modifications, epitranscriptomics remains in its infancy, methodological breakthroughs of the last decade have enabled identification of these modifications with such accuracy that their large-scale screening is rational [ 117 , 118 , 119 , 120 , 121 , 143 ]. Encouragingly, research findings suggest both m 6 A and A-to-I to act as contributors or even potential initiators and drivers for several cardiovascular physiological and pathological processes including cardiogenesis, angiogenesis, hypertension, hypertrophy, atherosclerosis, ischemia, ischemia-reperfusion, fibrosis, HF, congenital heart disease, stroke, aneurysms, as well as cardiac repair and regeneration [ 25 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 51 , 52 , 53 , 54 , 55 , 56 ]. Remarkably, the first indication for coronary atherosclerosis to be reflected in the m 6 A content of mRNAs and long non-coding RNAs of peripheral mononuclear cells with suggested involvement in its pathophysiology has just recently been reported [ 151 ].…”

“…Silencing or overexpression of enzymes controlling m 6 A abundance has revealed the role of m 6 A in driving immune reactivity, proliferation, apoptosis, and many intracellular processes including mRNA splicing, translation, and degradation [ 20 , 26 ], as well as miRNA biogenesis [ 27 ]. Moreover, reports from diverse fields of research [ 28 , 29 , 30 , 31 ], and in an array of cardiovascular pathologies [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ], provide evidence of m 6 A as a master post-transcriptional regulator.…”