Fine particulate matter 2.5 (PM2.5) exposure leads to the progress of pulmonary disease. It has been reported that N6-methyladenosine (m6A) modification was involved in various biological processes and diseases. However, the critical role of m6A modification in pulmonary disease during PM2.5 exposure remains elusive. Here, we revealed that lung inflammation and mucus production caused by PM2.5 were associated with m6A modification. Both in vivo and in vitro assays demonstrated that PM2.5 exposure elevated the total level of m6A modification as well as the methyltransferase like 3 (METTL3) expression. Integration analysis of m6A RNA immunoprecipitation-seq (meRIP-seq) and RNA-seq discovered that METTL3 up-regulated the expression level and the m6A modification of Interleukin 24 (IL24). Importantly, we explored that the stability of IL24 mRNA was enhanced due to the increased m6A modification. Moreover, the data from qRT-PCR showed that PM2.5 also increased YTH N6-Methyladenosine RNA Binding Protein 1 (YTHDF1) expression, and the up-regulated YTHDF1 augmented IL24 mRNA translation efficiency. Down-regulation of Mettl3 reduced Il24 expression and ameliorated the pulmonary inflammation and mucus secretion in mice exposed to PM2.5. Taken together, our finding provided a comprehensive insight for revealing the significant role of m6A regulators in the lung injury via METTL3/YTHDF1-coupled epitranscriptomal regulation of IL24.

细颗粒物 2.5 (PM2.5) 暴露会导致肺部疾病的进展。据报道，N6-甲基腺苷（m6A）修饰参与了各种生物过程和疾病。然而，在 PM2.5 暴露期间 m6A 修饰在肺部疾病中的关键作用仍然难以捉摸。在这里，我们发现由 PM2.5 引起的肺部炎症和粘液产生与 m6A 修饰有关。都在体内和体外测定表明，PM2.5 暴露提高了 m6A 修饰的总水平以及甲基转移酶样 3 (METTL3) 的表达。m6A RNA免疫沉淀序列（meRIP-seq）和RNA-seq的整合分析发现METTL3上调了白介素24（IL24）的表达水平和m6A修饰。重要的是，我们探讨了由于 m6A 修饰增加而增强了IL2 4 mRNA 的稳定性。此外，来自 qRT-PCR 的数据显示 PM2.5 还增加了YTH N6-甲基腺苷 RNA 结合蛋白 1 (YTHDF1)的表达，上调的 YTHDF1 增强了IL24 mRNA翻译效率。Mettl3 的下调降低了 Il24 的表达并改善了暴露于 PM2.5 的小鼠的肺部炎症和粘液分泌。总之，我们的发现为通过 METTL3/YTHDF1 偶联的 IL24 外转录调控揭示 m6A 调节剂在肺损伤中的重要作用提供了全面的见解。