RNA Methylation and Mental Health: Emerging Molecular Insights

Dear Colleagues,

RNA methylation, particularly N⁶-methyladenosine (m⁶A), has emerged as a key epigenetic mechanism regulating gene expression in the nervous system. By modulating RNA splicing, stability, translation, and localization, m⁶A and other modifications, such as N¹-methyladenosine (m¹A) and 5-methylcytosine (m⁵C), shape neuronal development, synaptic plasticity, and neurocircuit function. These processes are essential for cognition, emotion regulation, and stress responses.

Recent studies have revealed that the dysregulation of RNA methylation “writers” (e.g., METTL3, METTL14), “erasers” (e.g., FTO, ALKBH5), and “readers” (e.g., YTH domain proteins) is linked to psychiatric and neurodevelopmental disorders, including depression, schizophrenia, bipolar disorder, anxiety, and substance use disorders. Aberrant methylation patterns can alter neural gene expression programs, impair neurotransmission, and disrupt stress-adaptive pathways, contributing to disease susceptibility and symptom progression.

Advances in high-throughput sequencing and methylation mapping have enabled the precise profiling of RNA modifications in human brain tissue and disease models, uncovering disorder-specific signatures. These findings highlight RNA methylation regulators as promising biomarkers and potential therapeutic targets. The pharmacological modulation of RNA methylation machinery may open new avenues for precision psychiatry, offering treatments that target underlying molecular dysfunctions rather than symptoms alone.

This Special Issue highlights research and review articles that advance our understanding of the role of the epitranscriptome or RNA methylation in mental disorders.

Dr. Huiping Zhang
Guest Editor

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