Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Institutes of Integrative Medicine, Fudan University, Shanghai, China.
Front Immunol. 2021 Oct 19;12:740571. doi: 10.3389/fimmu.2021.740571. eCollection 2021.
Allergic asthma is well known as a common respiratory disorder comprising an allergic inflammatory nature and excessive immune characteristic. -methyladenosine (m6A) methylation is an RNA epigenetic modification that post-transcriptionally regulates gene expression and function by affecting the RNA fate. Currently, m6A methylation is gaining attention as a mechanism of immunoregulation. However, whether m6A methylation engages the pathological process of asthma remains uncertain. Here, we present the m6A methylomic landscape in the lung tissues of ovalbumin-induced acute asthma mice using MeRIP-seq and RNA-seq. We identified 353 hypermethylated m6A peaks within 329 messenger RNAs (mRNAs) and 150 hypomethylated m6A peaks within 143 mRNAs in the lung tissues of asthmatic mice. These differentially methylated mRNAs were found to be involved in several immune function-relevant signaling pathways. In addition, we predicted 25 RNA-binding proteins that recognize the differentially methylated peak sites by exploring public databases, and the roles of these proteins are mostly related to mRNA biogenesis and metabolism. To further investigate the expression levels of the differentially methylated genes, we performed combined analysis of the m6A methylome and transcriptome data and identified 127 hypermethylated mRNAs (107 high and 20 low expression) and 43 hypomethylated mRNAs with differential expressions (9 high and 34 low expression). Of these, there are a list of mRNAs involved in immune function and regulation. The present results highlight the essential role of m6A methylation in the pathogenesis of asthma.
变应性哮喘是一种常见的呼吸道疾病,其特征为过敏性炎症和过度免疫。-甲基腺苷(m6A)甲基化是一种 RNA 表观遗传修饰,通过影响 RNA 命运,在后转录水平上调节基因表达和功能。目前,m6A 甲基化作为一种免疫调节机制受到关注。然而,m6A 甲基化是否参与哮喘的病理过程尚不清楚。在这里,我们使用 MeRIP-seq 和 RNA-seq 展示了卵清蛋白诱导的急性哮喘小鼠肺组织中的 m6A 甲基组图谱。我们在哮喘小鼠的肺组织中鉴定了 353 个高甲基化 m6A 峰,这些峰位于 329 个信使 RNA(mRNA)内,以及 150 个低甲基化 m6A 峰,这些峰位于 143 个 mRNA 内。这些差异甲基化的 mRNA 被发现参与了几个与免疫功能相关的信号通路。此外,我们通过探索公共数据库,预测了 25 个识别差异甲基化峰的 RNA 结合蛋白,这些蛋白的作用大多与 mRNA 生物发生和代谢有关。为了进一步研究差异甲基化基因的表达水平,我们对 m6A 甲基组和转录组数据进行了联合分析,鉴定了 127 个高甲基化 mRNA(107 个高表达和 20 个低表达)和 43 个低甲基化 mRNA(9 个高表达和 34 个低表达)。其中有一系列涉及免疫功能和调节的 mRNAs。本研究结果突出了 m6A 甲基化在哮喘发病机制中的重要作用。