Regulatory roles of N6-methyladenosine (m⁶A) 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 (m⁶A) 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. m⁶A 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 m⁶A modification and m⁶A-associated proteins to a wide range of human diseases. However, the impact of m⁶A on mRNA metabolism and its pathological connection between m⁶A 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 m⁶A exerts its activities and address new discoveries that highlight m⁶A’s diverse involvement in gene expression regulation. We discuss m⁶A deposition on mRNA and its consequences on degradation, translation, and transcription, as well as m⁶A 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 m⁶A regulators in diseases may have therapeutic advantages.