Novel Insights into The Roles of N(6)-methyladenosine (m(6)A) Modification and Autophagy in Human Diseases

Autophagy is an evolutionarily conserved cellular degradation and recycling process. It is important for maintaining vital cellular function and metabolism. Abnormal autophagy activity can cause the development of various diseases. N(6)-methyladenosine (m(6)A) methylation is the most prevalent and abundant internal modification in eukaryotes, affecting almost all aspects of RNA metabolism. The process of m(6)A modification is dynamic and adjustable. Its regulation depends on the regulation of m(6)A methyltransferases, m(6)A demethylases, and m(6)A binding proteins. m(6)A methylation and autophagy are two crucial and independent cellular events. Recent studies have shown that m(6)A modification mediates the transcriptional and post-transcriptional regulation of autophagy-related genes, affecting autophagy regulatory networks in multiple diseases. However, the regulatory effects of m(6)A regulators on autophagy in human diseases are not adequately acknowledged. In the present review, we summarized the latest knowledge of m(6)A modification in autophagy and elucidated the molecular regulatory mechanisms underlying m(6)A modification in autophagy regulatory networks. Moreover, we discuss the potentiality of m(6)A regulators serving as promising predictive biomarkers for human disease diagnosis and targets for therapy. This review will increase our understanding of the relationship between m(6)A methylation and autophagy, and provide novel insights to specifically target m(6)A modification in autophagy-associated therapeutic strategies.