Epitranscriptomics, the study of dynamic co- or post-transcriptional modifications on RNA, has emerged as a vibrant field in neurobiology. Major advances in sequencing, computational biology, and imaging have revealed more than 170 RNA modifications, carried out by dedicated “writer,” “eraser,” and “reader” proteins. These modifications control RNA splicing, stability, nuclear export, translation, and their association with ribonucleoprotein (RNP) granules such as stress granules and processing bodies. RNA modifications have proven critical for cellular events like differentiation and synaptic plasticity, yet the precise mechanisms by which they influence neural function—and how they respond to genetic, environmental, and toxic insults—remain incompletely understood. Evidence is growing that dysregulation of editing proteins may be partially compensated by other members of their ensembles, masking dynamic changes, and that their lack of target specificity introduces additional complexity.

Recent studies link disrupted epitranscriptomic regulation not only to cancer but increasingly to neurodegenerative disorders and their potential for therapeutic intervention. Technological innovations such as DART-FISH, expansion microscopy, live-cell imaging, and in vivo two-photon microscopy now allow visualization of single RNA molecules, their modifications , and RNP granules in real time within neurons. This has highlighted the importance of spatial distribution and local transport of RNAs in axons and dendrites for neuronal protein synthesis and function. Modifications such as N6-methyladenosine (m6A) and pseudouridine (Ψ) are being implicated in assembly of transport granules, RNA–protein interactions, and the regulation of transcript stability. Nevertheless, crucial questions remain about how these modifications affect RNA trafficking, anchoring, and translation in neural processes, especially in disease or after exposure to neurotoxicants and environmental contaminants such as per- and polyfluoroalkyl substances (PFAS).

This Research Topic aims to gather manuscripts investigating RNA modifications that impact RNA trafficking, stability, translation, and RNP granule dynamics within the central and peripheral nervous systems. We seek studies spanning genetic and age-related disorders, pathogen-driven diseases, and environmental exposures including heavy metals, pesticides, nerve agents, and “forever chemicals” like PFAS. We particularly welcome work exploring the manipulation of RNA targets and the functional implications for neurodegeneration, neuroimmunology, and therapy. Broader studies reporting true positive changes in the global epitranscriptome are also encouraged as the field works toward leveraging RNA modifications for higher-specificity therapeutics.

This Research Topic covers the roles and regulation of RNA modifications in neural contexts, framed by both foundational discoveries and translational advances. To gather further insights, we welcome original research articles, reviews, perspectives, and methodological papers addressing, but not limited to, the following themes:

o Epitranscriptomic regulation of neuronal function and homeostasis
o RNA modifications governing neuronal RNA trafficking and local translation
o Responses to neurotoxicants, environmental exposures, and PFAS
o Epitranscriptomics in neuroinflammation, neuroimmunology, and neurodegeneration
o Imaging and methodology for analyzing RNA modifications and RNP granules
o Compensation, specificity, and redundancy among RNA modification enzymes
o Therapeutic targeting of epitranscriptomic changes in neurological disorders

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Epitranscriptomic Regulation in the Nervous System