Heyuan Branch, Guangdong Provincial Laboratory of Lingnan Modern Agricultural Science and Technology & Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding & Key Laboratory of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science, South China Agricultural University, Guangzhou, China.
South China Collaborative Innovation Center for Poultry Disease Control and Product Safety, Guangzhou, China.
Front Immunol. 2022 Apr 22;13:868892. doi: 10.3389/fimmu.2022.868892. eCollection 2022.
Avian Leukosis Virus Subgroup J (ALV-J) is a tumorigenic virus with high morbidity and rapid transmission. N6-methyladenosine (mA) is a common epigenetic modification that may be closely related to the pathogenicity of ALV-J. Currently, there are no reports on whether mA modification is related to ALV-J induced tumor formation. In this study, we used methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) to examine the differences in mA methylation and gene expression in normal livers and ALV-J-induced tumor livers systematically, with functional enrichment and co-expression analysis. The results identified 6,541 mA methylated peaks, mainly enriched in CDS, and more than 83% of the transcripts contained 1-2 mA peaks. For RNA-seq, 1,896 and 1,757 differentially expressed mRNAs and lncRNAs were identified, respectively. Gene enrichment analysis indicated that they may be involved in biological processes and pathways such as immunology-related and apoptosis. Moreover, we identified 17 lncRNAs, commonly existing in differently expressed methylome and transcriptome. Through co-expression analysis, 126 differentially expressed lncRNAs, and 18 potentially mA-related methyltransferases were finally identified and connected, suggesting that mA modifications might affect gene expression of lncRNAs and play a role in ALV-J induced tumor formation. This study provides the first comprehensive description of the mA expression profile in tumor livers induced by ALV-J infection in chickens, which provides a basis for studying the role of mA modification in ALV-J induced tumorigenesis. This study provides clues for studying the epigenetic etiology and pathogenesis of ALV-J.
禽白血病病毒 J 亚群(ALV-J)是一种高发病率和快速传播的致瘤病毒。N6-甲基腺苷(m6A)是一种常见的表观遗传修饰,可能与 ALV-J 的致病性密切相关。目前,尚无关于 m6A 修饰是否与 ALV-J 诱导的肿瘤形成有关的报道。在这项研究中,我们使用甲基化 RNA 免疫沉淀测序(MeRIP-seq)和 RNA 测序(RNA-seq)系统地研究了正常肝脏和 ALV-J 诱导的肿瘤肝脏中 m6A 甲基化和基因表达的差异,进行了功能富集和共表达分析。结果鉴定了 6541 个 m6A 甲基化峰,主要富集在 CDS 中,超过 83%的转录本包含 1-2 个 m6A 峰。对于 RNA-seq,分别鉴定了 1896 个和 1757 个差异表达的 mRNA 和 lncRNA。基因富集分析表明,它们可能参与免疫相关和凋亡等生物学过程和途径。此外,我们鉴定了 17 个普遍存在于差异表达的甲基组和转录组中的 lncRNA。通过共表达分析,最终确定并连接了 126 个差异表达的 lncRNA 和 18 个潜在的 m6A 相关甲基转移酶,表明 m6A 修饰可能影响 lncRNA 的基因表达,并在 ALV-J 诱导的肿瘤形成中发挥作用。本研究首次全面描述了 ALV-J 感染鸡诱导的肿瘤肝脏中 m6A 的表达谱,为研究 m6A 修饰在 ALV-J 诱导肿瘤发生中的作用提供了依据。本研究为研究 ALV-J 的表观遗传病因和发病机制提供了线索。