<scp>METTL14</scp> ‐Mediated <scp>m6A</scp> Modification of <scp>NEAT1_2</scp> Releases <scp>YBX1</scp> From Paraspeckles to Exacerbate Periodontitis

AIM: To investigate the role and epigenetic mechanism of methyltransferase 14 (METTL14)-mediated N6-adenylate methylation (m6A) modification of long non-coding RNAs (lncRNAs) in the pathogenesis of periodontitis. MATERIALS AND METHODS: ) was established using silk ligatures. Human periodontal ligament cells (PDLCs) were used for in vitro assays. MeRIP-seq, RNA-seq, RNA pull-down, mass spectrometry, RIP Co-IP and CUT&Tag were performed to elucidate the METTL14-NEAT1_2-YBX1 axis. RESULTS: METTL14 expression was significantly up-regulated in inflamed periodontal tissue. METTL14 deficiency alleviated alveolar bone destruction and suppressed IL-6 expression in vivo and in vitro. Mechanistically, METTL14 catalysed m6A modification of nuclear paraspeckle assembly transcript 1_2 (NEAT1_2), facilitating NEAT1_2 degradation. NEAT1_2-organised paraspeckles (PSPs) sequestered the transcription factor Y-box binding protein 1 (YBX1) under normal conditions. In periodontitis, METTL14-induced NEAT1_2 down-regulation triggered PSP disassembly, resulting in the translocation of YBX1 to the nucleus and increased IL-6 transcription. Neat1_2 knockdown exacerbated bone loss and neutralised the protective effect of METTL14 deficiency. CONCLUSION: METTL14-mediated m6A modification exacerbates periodontitis by disrupting NEAT1_2-dependent PSP sequestration of YBX1. This study identifies the METTL14-NEAT1_2 axis as a critical regulator of periodontal inflammation, suggesting that METTL14 is a potential therapeutic target for periodontitis.