METTL1‐Mediated M 7 G tRNA Modification Promotes Residual Liver Regeneration After Hepatectomy via Translational Control

作者：Manling Huang, Shuirong Lin, Shuirong Lin, Yutong Zhao, Jiale Chen, Linyuan Huang, Yuyao Liu, Zixin Huang, Dongmei An, Yifan Zhang, Zimin Song, Xin Yu, Yunpeng Hua, Jing Wang, Weiwei Wang, Yu Guo, Ming Kuang, Fang Wang, Shuibin Lin, Shuibin Lin, Shunli Shen · 发表于：Advanced Science · 年份：2025 · DOI：10.1002/advs.202507329 · 被引用次数：1 · 研究领域：RNA modifications and cancer、Kruppel-like factors research、Hippo pathway signaling and YAP/TAZ

Abstract Partial hepatectomy (PHx) has emerged as a primary therapeutic intervention for end‐stage liver pathologies. However, post‐hepatectomy liver failure (PHLF), a critical complication arising from inadequate regenerative capacity of the remnant liver, underscores the clinical imperative to understand molecular mechanisms governing hepatic regeneration. Through an integrative multi‐omics analysis in a murine 70% PHx model coupled with clinical correlation studies, the tRNA m 7 G methyltransferase METTL1 was identified as a pivotal regulator of post‐resection hepatic recovery. METTL1 exhibited significant temporal upregulation following PHx, with its expression profile positively correlating with favorable clinical outcomes in surgical patients. Genetic ablation of METTL1 substantially attenuated hepatocyte proliferation and compromised regenerative capacity, whereas its ectopic expression potentiated liver regeneration through enhanced translational efficiency. Mechanistic investigations revealed that METTL1‐mediated m 7 G tRNA modification orchestrates regenerative processes by selectively augmenting the translation of Hippo pathway effectors YAP/TAZ. Most importantly, modulation of the METTL1‐YAP/TAZ signaling axis successfully promotes liver regeneration after PHx. This study elucidates a previously unrecognized translational control mechanism underlying liver regeneration, proposing METTL1 as a promising molecular target for preventing PHLF through therapeutic enhanc...