RNA methylation in cell death: mechanisms and clinical applications

RNA methylation represents a critical epi-transcriptomic modification that regulates cell fate by modulating diverse aspects of RNA metabolism, including splicing, export, translation, and degradation. Among the best-characterized modifications are N⁶-methyladenosine (m⁶A), 5-methylcytosine (m⁵C), N⁷-methylguanosine (m⁷G), and N¹-methyladenosine (m¹A), which are dynamically regulated by specific writer, eraser and reader proteins. Dysregulation of these modifications perturbs multiple regulated cell death pathways, such as apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and cuproptosis, thereby promoting tumor progression, immune evasion, and therapeutic resistance. In this review, we summarize the molecular mechanisms by which RNA methylation shapes cell death programs and highlight its potential as a biomarker for cancer diagnosis and prognosis, as well as a promising target for therapeutic intervention.