Redox-sensitive N6-methyladenosine RNA epitranscriptomic mechanisms in environmental stress and hazard

Oxidative stress is a central driver of environmental stress responses and disease pathogenesis. Increasing evidence indicates that RNA epigenetic regulation, particularly N⁶-methyladenosine (m⁶A) modification, represents a critical interface linking redox imbalance to cellular dysfunction. Arsenic, a prototypical redox-active toxicant, provides a robust model for understanding how environmental oxidative stress disrupts m⁶A-mediated post-transcriptional control. Recent studies demonstrate that arsenic-induced redox perturbation reshapes the expression and activity of m⁶A writers (METTL3/METTL14), erasers (FTO/ALKBH5), and readers (YTHDF/YTHDC families), leading to widespread alterations in mRNA stability, translation, and metabolic reprogramming. Mechanistic findings from cellular and animal models implicate m⁶A-dependent pathways in modulating oxidative stress responses, mitochondrial function, inflammation, and senescence-biological processes fundamental to redox biology. These insights reveal that m⁶A is not merely a downstream marker of stress, but an active mediator of adaptive and maladaptive responses to redox disruption. Despite significant progress, population-level evidence and high-resolution mapping of RNA modifications under oxidative conditions remain limited. Future work integrating advanced epitranscriptomic profiling, multi-omics approaches, and exploration of additional RNA modifications (m⁷G, m¹A, m⁵C) will be essential for defining how redox-sensitive RNA regulation shapes disease risk. Collectively, this review highlights m⁶A modification as a dynamic regulatory node connecting environmental redox stress to gene expression control, providing new mechanistic insight and potential targets for intervention in redox-related diseases.