Regulatory Roles of N6-methyladenosine (mA) Methylation in RNA Processing and Non-communicable Diseases

Post-transcriptional RNA modification is an emerging epigenetic control mechanism in cells that is important in many different cellular and organismal processes. N6-methyladenosine (mA) is one of the most prevalent, prolific, and ubiquitous internal transcriptional alterations in eukaryotic mRNAs, making it an important topic in the field of Epigenetics. mA methylation acts as a dynamical regulatory process that regulates the activity of genes and participates in multiple physiological processes, by supporting multiple aspects of essential mRNA metabolic processes, including pre-mRNA splicing, nuclear export, translation, miRNA synthesis, and stability. Extensive research has linked aberrations in mA modification and mA-associated proteins to a wide range of human diseases. However, the impact of mA on mRNA metabolism and its pathological connection between mA and other non-communicable diseases, including cardiovascular disease, neurodegenerative disorders, liver diseases, and cancer remains in fragmentation. Here, we review the existing understanding of the overall role of mechanisms by which mA exerts its activities and address new discoveries that highlight mA's diverse involvement in gene expression regulation. We discuss mA deposition on mRNA and its consequences on degradation, translation, and transcription, as well as mA methylation of non-coding chromosomal-associated RNA species. This study could give new information about the molecular process, early detection, tailored treatment, and predictive evaluation of human non-communicable diseases like cancer. We also explore more about new data that suggests targeting mA regulators in diseases may have therapeutic advantages.