WTAP suppresses STAT3 via m6A methylation to regulate autophagy and inflammation in central nervous system injury.

Abstract

Central nervous system (CNS) repair after injury is a challenging process limited by inflammation and neuronal apoptosis. This study identifies Wilms' tumor 1-associating protein (WTAP) as a pivotal regulator of neuronal protection and repair through m6A methylation of STAT3 mRNA. By employing spinal cord injury (SCI) as a representative model of CNS injury, transcriptomic analyses reveal WTAP as a key mediator of pathways related to neuronal autophagy and inflammation regulation. WTAP enhances neuronal autophagy by suppressing STAT3 expression and activity, which inhibits the NLRP3 inflammatory pathway. Functional studies demonstrate that WTAP knockdown exacerbates neuronal apoptosis, whereas overexpression improves cell viability, autophagy, and motor recovery. In vivo, WTAP promotes SCI repair via m6A-mediated suppression of STAT3 and regulation of the NLRP3 signaling pathway, highlighting its therapeutic potential for CNS injury repair.