Redox-sensitive m⁶A epitranscriptomic remodeling in cadmium stress and toxicity

Environmental stressors that disrupt redox homeostasis pose a significant threat to metabolic balance, tissue integrity, and organismal development. Increasing evidence identifies N⁶-methyladenosine (m⁶A), a dynamic and stress-responsive RNA modification, as a central regulator that translates oxidative cues into functional changes in RNA metabolism and cellular behavior. Redox imbalance can recalibrate the activity, localization, and substrate selectivity of m⁶A writers, erasers, and readers, thereby reshaping transcriptomic programs that control inflammation, antioxidant defense, proteostasis, mitochondrial quality, and stress-adaptive cell fate decisions. These m⁶A-dependent responses manifest across diverse tissues, including the liver, kidney, pancreas, lung, brain, and reproductive organs, where they influence unfolded protein responses, β-cell resilience, epithelial plasticity, fibrotic remodeling, neurodegenerative processes, and gametogenic stability. m⁶A dysregulation also contributes to placental stress signaling, developmental vulnerability, and intergenerational transmission of metabolic and reproductive outcomes following environmental perturbation. In this work, we integrate emerging evidence to propose a unified framework illustrating how redox-sensitive m⁶A signaling orchestrates cellular and physiological responses to environmental stress, using cadmium as an exemplar due to its well-established role as an oxidative stress inducer. We highlight mechanistic convergence across tissues, note sources of exposure specificity, and discuss technological advances that are redefining the resolution of m⁶A mapping. Finally, we outline opportunities for leveraging m⁶A as a biomarker, mechanistic probe, and potential therapeutic target in the study of environmental cadmium stress and associated diseases.