Emerging Roles for DNA 6mA and RNA m6A Methylation in Mammalian Genome

Epigenetic methylation has been shown to play an important role in transcriptional regulation and disease pathogenesis. Recent advancements in detection techniques have identified DNA N6-methyldeoxyadenosine (6mA) and RNA N6-methyladenosine (m6A) as methylation modifications at the sixth position of adenine in DNA and RNA, respectively. While the distributions and functions of 6mA and m6A have been extensively studied in prokaryotes, their roles in the mammalian brain, where they are enriched, are still not fully understood. In this review, we provide a comprehensive summary of the current research progress on 6mA and m6A, as well as their associated writers, erasers, and readers at both DNA and RNA levels. Specifically, we focus on the potential roles of 6mA and m6A in the fundamental biological pathways of the mammalian genome and highlight the significant regulatory functions of 6mA in neurodegenerative diseases.