The m6A epitranscriptome on neural development and degeneration

N-6-methyladenosine (m(6)A) is the most prevalent, conserved, and abundant RNA modification of the mRNAs of most eukaryotes, including mammals. Similar to epigenetic DNA modifications, m(6)A has been proposed to function as a critical regulator for gene expression. This modification is installed by m(6)A methylation writers (Mettl3/Mettl14 methyltransferase complex), and it can be reversed by demethylase erasers (Fto and Alkbh5). Furthermore, m(6)A can be recognized by readers (Ythdf and Ythdc families), which may be interpreted to affect mRNA splicing, stability, translation or localization. Levels of m(6)A methylation appear to be highest in the brain, where it plays important functions during embryonic stem cell differentiation, brain development, and neurodevelopmental disorders. Depletion of the m(6)A methylation writer Mettl14 from mouse embryonic nervous systems prolongs cell cycle progression of radial glia and extends cortical neurogenesis into postnatal stages. Recent studies further imply that dysregulated m(6)A methylation may be significantly correlated with neurodegenerative diseases. In this review, we give an overview of m(6)A modifications during neural development and associated disorders, and provide perspectives for studying m(6)A methylation.

Automated summary

N-6-methyladenosine (m(6)A) is the most prevalent, conserved, and abundant RNA modification in the mRNAs of most eukaryotes, similar to epigenetic DNA modifications, it is proposed to be a critical regulator for gene expression. The installation and reversal of m(6)A modification are mediated by writers and erasers, while readers recognize and interpret the modification to affect mRNA processing and function. Studies suggest that dysregulated m(6)A methylation may be significantly correlated with neurodegenerative diseases, indicating its potential importance in neural development and disorders.