The m(6)A 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.