mRNA modifications in cardiovascular biology and disease: with a focus on m6A modification

Among several known RNA modifications, N-6-methyladenosine (m(6)A) is the most studied RNA epitranscriptomic modification and controls multiple cellular functions during development, differentiation, and disease. Current research advancements have made it possible to examine the regulatory mechanisms associated with RNA methylation and reveal its functional consequences in the pathobiology of many diseases, including heart failure. m(6)A methylation has been described both on coding (mRNA) and non-coding RNA species including rRNA, tRNA, small nuclear RNA and circular RNAs. The protein components which catalyze the m(6)A methylation are termed methyltransferase or 'm(6)A writers'. The family of proteins that recognize this methylation are termed 'm(6)A readers' and finally the enzymes involved in the removal of a methyl group from RNA are known as demethylases or 'm(6)A erasers'. At the cellular level, different components of methylation machinery are tightly regulated by many factors to maintain the m(6)A methylation dynamics. The m(6)A methylation process impacts different stages of mRNA metabolism and the biogenesis of long non-coding RNA and miRNA. Although, mRNA methylation was initially described in the 1970s, its regulatory roles in various diseases, including cardiovascular diseases are broadly unexplored. Recent investigations suggest the important role of m(6)A mRNA methylation in both hypertrophic and ischaemic heart diseases. In the present review, we evaluate the significance of m(6)A methylation in the cardiovascular system, in cardiac homeostasis and disease, all of which may help to improve therapeutic intervention for the treatment of heart failure. RNA methylation in cardiovascular diseases: altered m(6)A RNA (coding and non-coding RNA) methylation is identified during different cardiovascular diseases. Increased cardiac hypertrophy is observed following METTL3 overexpression. In contrast, reduced FTO level was seen in mice following myocardial infarction. Increased cardiac fibroblasts activation or increased atherosclerotic plaques were also co-related with m(6)A RNA methylation.

Automated summary

m(6)A methylation is a highly studied RNA modification that plays a crucial role in cellular functions during development, differentiation, and disease. It is found in different RNA species and is regulated by various enzymes and proteins. In cardiovascular diseases, m(6)A methylation is associated with cardiac hypertrophy, myocardial infarction, and atherosclerosis.