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Updated: Nov 9, 2025

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Mettl14-Mediated m6A Modification Facilitates Liver Regeneration by Maintaining Endoplasmic Reticulum Homeostasis

Xiaoyue Cao1, Yuke Shu1, Yuwei Chen1

  • 1Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu, China.

Cellular and Molecular Gastroenterology and Hepatology
|April 13, 2021
PubMed
Abstract

Insights

Mettl14 is crucial for liver regeneration, controlling m6A methylation of genes involved in protein processing and ER stress. Its absence leads to hepatocyte death and impaired liver repair.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Hepatology

Background:

  • N6-methyladenosine (m6A) is a key mRNA modification in mammals.
  • Its function in liver regeneration remains largely uncharacterized.

Purpose of the Study:

  • To investigate the role of m6A and its regulators in liver regeneration.
  • To elucidate the underlying molecular mechanisms.

Main Methods:

  • Transcriptome-wide m6A sequencing in regenerating mouse liver.
  • Generation of hepatocyte-specific Mettl3- and Mettl14-deficient mice.
  • In vitro and in vivo biochemical assays.

Main Results:

  • m6A levels dynamically changed during liver regeneration.
  • Mettl14 deficiency, but not Mettl3 deficiency, severely impaired liver regeneration.
  • Mettl14-deficient hepatocytes showed G1 cell cycle arrest, necrosis, and ER stress due to reduced levels of key protein processing genes.

Conclusions:

  • Mettl14 plays an essential role in liver regeneration.
  • This function is mediated by m6A-dependent regulation of ER protein processing and stress response pathways.
Keywords:
Endoplasmic Reticulum StressLiver RegenerationMettl14N(6)-methyladenosine

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