Comprehensive analysis of transcriptome-wide M6A methylation for hepatic ischaemia reperfusion injury in mice

Epigenetics. 2023 Dec;18(1):2201716. doi: 10.1080/15592294.2023.2201716.

Abstract

N6-Methyladenosine (m6A) plays key roles in the regulation of biological functions and cellular mechanisms for ischaemia reperfusion (IR) injury in different organs. However, little is known about the underlying mechanisms of m6A-modified mRNAs in hepatic IR injury. In mouse models, liver samples were subjected to methylated RNA immunoprecipitation with high-throughput sequencing (MeRIP-seq) and RNA sequencing (RNA-seq). In total, 16917 m6A peaks associated with 4098 genes were detected in the sham group, whereas 21,557 m6A peaks associated with 5322 genes were detected in the IR group. There were 909 differentially expressed m6A peaks, 863 differentially methylated transcripts and 516 differentially m6A modification genes determined in both groups. The distribution of m6A peaks was especially enriched in the coding sequence and 3'UTR. Furthermore, we identified a relationship between differentially m6A methylated genes (fold change≥1.5/≤ 0.667, p value≤0.05) and differentially expressed genes (fold change≥1.5 and p value≤0.05) to obtain three overlapping predicted target genes (Fnip2, Phldb2, and Pcf11). Our study revealed a transcriptome-wide map of m6A mRNAs in hepatic IR injury and might provide a theoretical basis for future research in terms of molecular mechanisms.

Keywords: MeRIP-seq; N6-methyladenosine; hepatic ischaemia reperfusion injury; methyltransferase; posttranscriptional regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • DNA Methylation
  • Mice
  • Protein Processing, Post-Translational
  • RNA, Messenger / genetics
  • Reperfusion Injury* / genetics
  • Transcriptome*

Substances

  • 3' Untranslated Regions
  • RNA, Messenger

Grants and funding

This work was supported by the Outstanding Youth Training Fund from Academician Yu Weihan of Harbin Medical University (2014); Scientific Foundation of the First Affiliated Hospital of Harbin Medical University under Grant 2019L01, HYD2020JQ0007; Heilongjiang Postdoctoral Foundation under Grant LBH-Z11066; Natural Science Foundation of Heilongjiang Province of China under Grant LC2018037 and the National Scientific Foundation of China under Grant 81100305, 81470876 and 81270527.