Mettl14-Mediated m6A Modification Facilitates Liver Regeneration by Maintaining Endoplasmic Reticulum Homeostasis
Xiaoyue Cao, Yuke Shu, Yuwei Chen, Qing Xu, Gang Guo, Zhenru Wu, Mingyang Shao, Yongjie Zhou, Menglin Chen, Yuping Gong, Chuan Li, Yujun Shi, Hong Bu
Abstract
BACKGROUND & AIMS: A), the most prevalent and dynamic posttranscriptional methylation modification of mammalian mRNA, is involved in various biological processes, but its role in liver regeneration has not been characterized. METHODS: A in regenerating mouse liver. Next, we generated hepatocyte-specific Mettl3- or Mettl14-deficient mice and investigated their role in liver regeneration. A series of biochemical experiments in vitro and in vivo was further performed to investigate potential mechanisms. RESULTS: A-hypomethylated, and their mRNA and protein levels were subsequently decreased, resulting in unresolved ER stress, hepatocyte death, and inhibited proliferation. CONCLUSIONS: A-dependent manner.