N6-methyladenosine-methylomic landscape of lung tissues of mice with chronic obstructive pulmonary disease

Front Immunol. 2023 Mar 28:14:1137195. doi: 10.3389/fimmu.2023.1137195. eCollection 2023.

Abstract

Chronic obstructive pulmonary disease (COPD), a common respiratory disease, can be divided into stable phase and acute exacerbation phase (AECOPD) and is characterized by inflammation and hyper-immunity. Methylation of N6-methyladenosine (m6A) is an epigenetic modification that regulates the expression and functions of genes by influencing post-transcriptional RNA modifications. Its influence on the immune regulation mechanism has attracted great attention. Herein, we present the m6Amethylomic landscape and observe how the methylation of m6A participates in the pathological process of COPD. The m6A modification of 430 genes increased and that of 3995 genes decreased in the lung tissues of mice with stable COPD. The lung tissues of mice with AECOPD exhibited 740 genes with hypermethylated m6A peak and 1373 genes with low m6A peak. These differentially methylated genes participated in signaling pathways related to immune functions. To further clarify the expression levels of differentially methylated genes, RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-sequencing data were jointly analyzed. In the stable COPD group, 119 hypermethylated mRNAs (82 upregulated and 37 downregulated mRNAs) and 867 hypomethylated mRNAs (419 upregulated and 448 downregulated mRNAs) were differentially expressed. In the AECOPD group, 87 hypermethylated mRNAs (71 upregulated and 16 downregulated mRNAs) and 358 hypomethylated mRNAs (115 upregulated and 243 downregulated mRNAs) showed differential expression. Many mRNAs were related to immune function and inflammation. Together, this study provides important evidence on the role of RNA methylation of m6A in COPD.

Keywords: COPD; MeRIP-seq; N6-methyladenosine; lung tissue; m6A; mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine
  • Animals
  • Inflammation
  • Lung
  • Mice
  • Pulmonary Disease, Chronic Obstructive* / genetics
  • RNA
  • RNA, Messenger / genetics

Substances

  • RNA
  • RNA, Messenger
  • Adenosine

Grants and funding

This study was jointly supported by the Outstanding Young Scientists Fund of Xinjiang Uygur Autonomous Region Natural Science Foundation project (Project No: 2022D01E28), the Young Scientists Fund of Xinjiang Uygur Autonomous Region Natural Science Foundation project (Project No: 2022D01C176 and 2022D01C179), the Xinjiang Key Laboratory of Respiratory Disease Research Open Subjects (Project No: ZYYHX202104), the National Natural Science Foundation Regional Fund Project (Project No: 82160844 and 81960848), and the Xinjiang Uyghur Autonomous Region Key Laboratory Open Subjects[Project No: 2021D0423].