The m6A epitranscriptome on neural development and degeneration

• Published in: Journal of biomedical science 2021-05, Vol.28 (1), p.1-40, Article 40
• Main Authors: Yen, Ya-Ping, Chen, Jun-An
• Format: Article
• Language: English
• Subjects: Brain; Brain stem; Cell cycle; Cell differentiation; Cell division; Degeneration; Deoxyribonucleic acid; Depletion; Differentiation (biology); Disorders; DNA; DNA methylation; Embryogenesis; Embryonic development; Embryonic stem cells; Epigenetic inheritance; Epigenetics; Epitranscriptome; Eukaryotes; Gene expression; Genes; Homeostasis; Insects; Localization; m6A; Mammals; Medical research; Medicine, Experimental; Messenger RNA; Methylation; Methyltransferase; Methyltransferases; mRNA stability; Mutation; N6-methyladenosine; Nervous system diseases; Neural development; Neurodegeneration; Neurodegenerative diseases; Neurodevelopmental disorders; Neurogenesis; Neuronal-glial interactions; Physiological aspects; Proteins; Radial glial cells; Review; RNA; RNA modification; Roles; Splicing; Stem cells
• ISSN: 1423-0127; 1021-7770; 1423-0127
• DOI: 10.1186/s12929-021-00734-6

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.