m<sup>6</sup>A in RNA: a key regulator of brain development, function and disease.
review · Level V
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- Record sourced from PubMed, PMID 42332080.
- Also identified by DOI 10.1038/s41583-026-01056-y.
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Abstract
Epitranscriptomic regulation of cellular RNAs is a major mechanism of gene expression control in the brain. N<sup>6</sup>-Methyladenosine (m<sup>6</sup>A) 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, m<sup>6</sup>A 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 m<sup>6</sup>A is deposited, interpreted and dynamically regulated, and integrate recent advances to present a unified framework for its function in neural cells. We discuss how m<sup>6</sup>A 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.