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 N 6 -methyladenosine (m 6 A) 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 m 6 A-mediated post-transcriptional control. Recent studies demonstrate that arsenic-induced redox perturbation reshapes the expression and activity of m 6 A 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 m 6 A-dependent pathways in modulating oxidative stress responses, mitochondrial function, inflammation, and senescence—biological processes fundamental to redox biology. These insights reveal that m 6 A 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 (m 7 G, m 1 A, m 5 C) will be essential for defining how redox-sensitive RNA regulation shapes disease risk. Collectively, this review highlights m 6 A 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. • Arsenic induces aberrant RNA m 6 A modification, disrupting mRNA stability, translation, and metabolic homeostasis. • METTL3, FTO, YTHDF/YTHDC are dynamically altered under arsenic stress, mediating neurotoxicity, reproductive injury, and developmental impairment. • m 6 A-regulated oxidative stress, mitochondrial dysfunction, and cellular senescence as central pathways in arsenic-induced toxicity. • m 6 A-based biomarkers and metabolic cofactor supplementation (e.g., folate, NAD + ) may offer novel prevention and therapeutic potential. • Future research should expand beyond m 6 A to other RNA modifications (m 7 G, m 1 A, m 5 C) and explore translational strategies for risk assessment.