Epitranscriptomics in kidney disease: insights and therapeutic potential

Epitranscriptomic regulation, particularly N6-methyladenosine (m⁶A) RNA methylation, has emerged as a pivotal layer of gene expression control, complementing traditional epigenetic mechanisms. As the most prevalent internal modification in eukaryotic messenger RNA, m⁶A dynamically modulates RNA splicing, stability, translation, and localization through the coordinated actions of writer, eraser, and reader proteins. Recent studies have illuminated the critical role of m⁶A in kidney disease and renal fibrosis. Dysregulation of m⁶A machinery has been shown to influence key pathogenic pathways in kidney disease development. Moreover, m⁶A-modified noncoding RNAs further integrate epitranscriptomic signals into fibrogenic and immune regulatory networks. Therapeutically, targeting m⁶A pathways offers promising avenues, with small-molecule inhibitors, RNA-based therapeutics, and clustered regularly interspaced short palindromic repeats (CRISPR)-based m⁶A editing technologies under active investigation. However, challenges remain in achieving tissue-specific modulation and avoiding systemic toxicity. This review synthesizes current knowledge on m⁶A-mediated regulation in kidney disease, highlighting mechanistic insights, disease-specific alterations, and emerging therapeutic strategies. As the field of epitranscriptomics continues to evolve, m⁶A represents a compelling frontier for understanding renal pathophysiology and developing precision therapies.