Role of m6A Methylation in the Occurrence and Development of Heart Failure

Abstract

N6-methyladenosine (m6A) RNA methylation is one of the most common epigenetic modifications in RNA nucleotides. It is known that m6A methylation is involved in regulation, including gene expression, homeostasis, mRNA stability and other biological processes, affecting metabolism and a variety of biochemical regulation processes, and affecting the occurrence and development of a variety of diseases. Cardiovascular disease has high morbidity, disability rate and mortality in the world, of which heart failure is the final stage. Deeper understanding of the potential molecular mechanism of heart failure and exploring more effective treatment strategies will bring good news to the sick population. At present, m6A methylation is the latest research direction, which reveals some potential links between epigenetics and pathogenesis of heart failure. And m6A methylation will bring new directions and ideas for the prevention, diagnosis and treatment of heart failure. The purpose of this paper is to review the physiological and pathological mechanisms of m6A methylation that may be involved in cardiac remodeling in heart failure, so as to explain the possible role of m6A methylation in the occurrence and development of heart failure. And we hope to help m6A methylation obtain more in-depth research in the occurrence and development of heart failure.

RNA binding proteins as mediators of pathological cardiac remodeling

“…m6A has been implicated to be an important target as repressed m6A levels have shown to attenuate fibrosis via altered RNA splicing, translation and degradation (Mathiyalagan et al, 2019;Chen et al, 2021). Some examples of RBPs that recognize m6A-modified mRNA are YT521-B homology (YTH), heterogenous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) and insulin-like growth factor 2 mRNA-binding protein (IGF2BP) domain (Qin et al, 2020;Fan and Hu, 2022). Heterogenous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) is also suggested to regulate cardiac homeostasis and hypertrophy via N6 methyladenosine mRNA methylase (METTL3) and m6A switch recognition and alternative splicing events (Qin et al, 2020;Fan and Hu, 2022).…”

“…Some examples of RBPs that recognize m6A-modified mRNA are YT521-B homology (YTH), heterogenous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) and insulin-like growth factor 2 mRNA-binding protein (IGF2BP) domain ( Qin et al, 2020 ; Fan and Hu, 2022 ). Heterogenous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) is also suggested to regulate cardiac homeostasis and hypertrophy via N6 methyladenosine mRNA methylase (METTL3) and m6A switch recognition and alternative splicing events ( Qin et al, 2020 ; Fan and Hu, 2022 ). RBPs also contribute to the regulation of RNA m5C methylation, dysregulation of which is closely associated with CVD ( Balachander et al, 2023 ).…”

Roles of rRNA N‐methyladenosine modification in the function of ribosomes

“…Through the function of the m6A recognition proteins, m6A methylation is involved in various biological processes such as cell differentiation, embryonic development, X chromosome inactivation, environmental stress, and the occurrence and spread of various diseases. [53][54][55][56][57] However, there are still many challenging issues to be clarified before the epigenetic regulation of m6A in RNA metabolism is fully understood.…”

N6-Methyladenosine in Vascular Aging and Related Diseases: Clinical Perspectives

“…HF is associated with deregulated epigenetic processes and abnormal gene expression [197]. Especially, RNA m 6 A methylation has been well-documented to participate in the development of HF [185,198]. m 6 A levels in human, pig, and mouse failing hearts are increased compared to those in normal controls [182].…”