Microglial METTL14 mediated m⁶A regulation of ATG13 promotes autophagy and functional recovery after spinal cord injury

Spinal cord injury (SCI) causes severe neurological deficits and remains difficult to treat, in part because persistent neuroinflammation limits tissue repair and functional recovery. Although N6-methyladenosine (m⁶A) modification regulates RNA metabolism in diverse biological contexts, its role in microglial responses after SCI remains unclear. Here we show that global m⁶A levels and expression of the methyltransferase METTL14 increase in the injured spinal cord two weeks after SCI, together with enrichment of autophagy-related pathways. Integrated MeRIP-seq and transcriptomic analyses identify autophagy-related protein 13 (ATG13) as a key m⁶A-modified target. In microglia, METTL14 knockdown impairs autophagy and increases proinflammatory cytokine expression, whereas METTL14 overexpression enhances autophagic activity and suppresses inflammatory responses. In vivo, viral overexpression of METTL14 improves neurological recovery after SCI. These findings identify METTL14 as an important regulator of microglial autophagy and neuroinflammation, at least in part through m⁶A-dependent regulation of ATG13, and suggest that epitranscriptomic regulation may provide a potential therapeutic avenue for spinal cord repair. METTL14-mediated m⁶A regulation of ATG13 uncovers a novel epitranscriptomic mechanism linking microglial autophagy and inflammation control after spinal cord injury.