Among several known
RNA modifications,
N6-methyladenosine (m6A) 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.
m6A 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
m6A methylation are termed
methyltransferase or '
m6A writers'. The family of
proteins that recognize this methylation are termed '
m6A readers' and finally the
enzymes involved in the removal of a methyl group from
RNA are known as demethylases or '
m6A erasers'. At the cellular level, different components of methylation machinery are tightly regulated by many factors to maintain the
m6A methylation dynamics. The
m6A 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
m6A mRNA methylation in both hypertrophic and ischaemic
heart diseases. In the present review, we evaluate the significance of
m6A 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
m6A 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 m6A RNA methylation.