N⁶-methyladenosine RNA methylation: From regulatory mechanisms to potential clinical applications

Epitranscriptomics has emerged as another level of epigenetic regulation similar to DNA and histone modifications. N⁶-methyladenosine (m⁶A) is one of the most prevalent and abundant posttranscriptional modifications, widely distributed in many biological species. The level of N⁶-methyladenosine RNA methylation is dynamically and reversibly regulated by distinct effectors including methyltransferases, demethylases, histone modification and metabolites. In addition, N⁶-methyladenosine RNA methylation is involved in multiple RNA metabolism pathways, such as splicing, localization, translation efficiency, stability and degradation, ultimately affecting various pathological processes, especially the oncogenic and tumor-suppressing activities. Recent studies also reveal that N⁶-methyladenosine modification exerts the function in immune cells and tumor immunity. In this review, we mainly focus on the regulatory mechanisms of N⁶-methyladenosine RNA methylation, the techniques for detecting N⁶-methyladenosine methylation, the role of N⁶-methyladenosine modification in cancer and other diseases, and the potential clinical applications.