The m⁶A epitranscriptome on neural development and degeneration

N⁶-methyladenosine (m⁶A) is the most prevalent, conserved, and abundant RNA modification of the mRNAs of most eukaryotes, including mammals. Similar to epigenetic DNA modifications, m⁶A has been proposed to function as a critical regulator for gene expression. This modification is installed by m⁶A methylation "writers" (Mettl3/Mettl14 methyltransferase complex), and it can be reversed by demethylase "erasers" (Fto and Alkbh5). Furthermore, m⁶A can be recognized by "readers" (Ythdf and Ythdc families), which may be interpreted to affect mRNA splicing, stability, translation or localization. Levels of m⁶A 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 m⁶A 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 m⁶A methylation may be significantly correlated with neurodegenerative diseases. In this review, we give an overview of m⁶A modifications during neural development and associated disorders, and provide perspectives for studying m⁶A methylation.