m6A in RNA: a key regulator of brain development, function and disease

Abstract

Epitranscriptomic regulation of cellular RNAs is a major mechanism of gene expression control in the brain. N6-Methyladenosine (m6A) is installed on thousands of mRNAs and non-coding RNAs, where it functions as a context-dependent regulator of RNA–protein interactions to control the amplitude and kinetics of gene expression. In the nervous system, m6A is critical for neurodevelopment, synaptic plasticity and adaptive responses to physiological stimuli, and its dysregulation has been linked to various brain disorders. In this Review, we present a comprehensive synthesis of how m6A is deposited, interpreted and dynamically regulated, and integrate recent advances to present a unified framework for its function in neural cells. We discuss how m6A coordinates RNA stability, translation, localization and chromatin-associated processes across developmental and adult contexts and how disruption of these pathways contributes to neurological disease. Finally, we explore challenges and future directions for the field. N6-Methyladenosine (m6A) is installed on many mRNAs and non-coding RNAs and regulates gene expression by affecting RNA–protein interactions. In this Review, Enakshi Sivasudhan and Kate Meyer discuss how m6A is dynamically regulated and interpreted, and examine its role in brain function and disorders.