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. This work was supported by the following grants: President’s Foundation of Nanfang Hospital, Southern Medical University (Grant No. 2023A024); Natural Science Foundation of Guangdong Province (Grant No. 2023A1515010565). Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China Haoxin Lian, Lijia Chen, Tianwei Wang, Ruqin Guo, Hao Ma, Zhiping Huang, Hui Jiang & Zucheng Huang Department of Plastic and Cosmetic Surgery, Foshan Sanshui District People’s Hospital (Sanshui Hospital, Zhujiang Hospital, Southern Medical University), Foshan, China Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, China Correspondence to Junhao Liu, Hui Jiang or Zucheng Huang.

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To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. Lian, H., Chen, L., Wang, T. et al. Microglial METTL14 mediated m⁶A regulation of ATG13 promotes autophagy and functional recovery after spinal cord injury.