m6A RNA Methylation in Psychiatric Disorders: An Emerging Epitranscriptomic Axis.

Abstract

N⁶-methyladenosine (m⁶A) is the most prevalent internal modification in eukaryotic messenger RNA (mRNA) and plays a vital role in post-transcriptional gene regulation. In recent years, m⁶A has emerged as a pivotal epitranscriptomic signal involved in neural development, synaptic remodeling, and the molecular pathophysiology of neuropsychiatric disorders. In this review, we summarize the mechanisms underlying the deposition, removal, and recognition of m⁶A by dedicated methyltransferases, demethylases, and RNA-binding proteins. We further explore how these dynamic modifications influence neuronal differentiation and memory formation. Recent studies have linked aberrant m⁶A regulation to psychiatric conditions such as depression, anxiety, schizophrenia, and bipolar disorder. Additionally, we discuss how pharmacological or genetic modulation of m⁶A pathways may promote adaptive neural plasticity and enhance cognitive and emotional resilience. Despite these promising findings, significant challenges remain in achieving spatial and temporal specificity while minimizing off-target effects in the brain. Therefore, we advocate for more in-depth investigations into m⁶A function within developmentally defined neural circuits to better understand its enduring role in maintaining neural homeostasis.