RNA Regulation Mediated By m6A Readers in the Nervous System

Recent studies have revealed that thousands of cellular mRNAs are susceptible to methylation of their adenosine residues to form a modified base called N⁶-methyladenosine, or m⁶A. m⁶A is particularly abundant within the brain and has recently been shown to regulate neurogenesis and neurodevelopment. However, the mechanisms through which m⁶A regulates gene expression in the developing brain are poorly understood. One major mechanism through which m⁶A regulates mRNAs is by recruiting m⁶A binding proteins, or “readers,” which control a variety of mRNA regulatory processes, such as mRNA stability, export, and translation. However, the proteins that recognize m⁶A in neurons and their roles in neurodevelopment are unknown. Here, we identify a neurodevelopmentally-enriched m⁶A reader which recognizes m⁶A through a unique mode of binding and influences mRNA translation and stability. Depletion of this reader impacts cellular proliferation, suggesting a potential mechanism through which m⁶A may influence cell cycle regulation during brain development.