m6A RNA Methylation in Psychiatric Disorders: An Emerging Epitranscriptomic Axis
Ambrose Loc Ngo, Linda Nguyen, Niki Gharavi Alksari, Huiping Zhang
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.