The Role of N⁶-Methyladenosine Modification in Health and Disease

Emerging evidence highlights that N⁶-methyladenosine (m⁶A), the most prevalent internal RNA modification in eukaryotes, serves as a critical epitranscriptomic regulator of RNA metabolism. This posttranscriptional modification modulates alternative splicing, nuclear export, stability, and translation, thereby regulating various physiological processes. Notably, dysregulation of m⁶A-associated modifiers (writers/erasers/readers) is implicated in a variety of diseases, such as metabolic disorders and cancer. Despite the rapid progress of m⁶A-mediated emerging therapeutic strategies, there remains an imperative to bridge the gap between basic epitranscriptomics and clinical application. This review systematically depicts recent advances in understanding m⁶A-mediated epitranscriptomic regulation, with particular focus on its dual role in maintaining cellular homeostasis and driving disease progression upon dysregulation, provides a dedicated exploration of m⁶A-regulated mitochondrial remodeling, and outlines cutting-edge technologies for m⁶A mapping and inhibitors targeting m⁶A modifiers. Furthermore, we conduct an in-depth exploration of the existing limitations and therapeutic potential associated with targeting m⁶A modification. Acting as a pivotal link between epitranscriptomics and medicine, m⁶A modification provides novel perspectives for developing precision interventions in complex human diseases.