Decoding m6A RNA methylation in kidney disorders: from molecular insights to therapeutic strategies
Qinfan Yao, Yitong Chen, Xinyi Zhang, Lefeng Wang, Jingyi Li, Junhao Lv, Jianghua Chen, Dajin Chen
Abstract
N6-methyladenosine (m6A), the most abundant internal modification in eukaryotic messenger RNA (mRNA) and long noncoding RNA (lncRNA), is dynamically modulated by methyltransferases (“writers”), demethylases (“erasers”), and binding proteins (“readers”). As a central epitranscriptomic regulator, m6A governs RNA stability, splicing, translation, and degradation, thereby orchestrating a wide range of physiological and pathological pathways. Accumulating evidence has underscored its pivotal involvement in the pathogenesis of kidney disorders. This review delineates the regulatory landscape of m6A methylation across various kidney diseases, with emphasis on diabetic nephropathy (DN), acute kidney injury (AKI), chronic kidney disease (CKD), focal segmental glomerulosclerosis (FSGS), lupus nephritis (LN), hyperuricemic nephropathy (HN), autosomal dominant polycystic kidney disease (ADPKD), and clear cell renal cell carcinoma (ccRCC). Disease-specific alterations in m6A levels and the expression patterns of core regulators, including METTL3, METTL14, FTO, ALKBH5, YTH domain proteins, and IGF2BPs, are systematically summarized. By elucidating their roles in inflammation, fibrosis, apoptosis, and metabolic imbalance, this review highlights the translational potential of m6A-centric interventions and offers novel insights into epitranscriptomic regulation within renal pathophysiology.