Transcriptome-Wide Dynamics of m(6)A Methylation in Tumor Livers Induced by ALV-J Infection in Chickens.
Transcriptome-Wide Dynamics of m(6)A Methylation in Tumor Livers Induced by ALV-J Infection in Chickens.
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鸡 ALV-J 感染诱导的肿瘤肝脏 m6A 甲基化的全转录组动态
DOI：
10.3389/fimmu.2022.868892
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发表时间：
2022
影响因子：
7.3
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中科院分区：
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J亚群禽白血病病毒（ALV-J）是一种发病率高、传播快的致瘤病毒。N6-甲基腺苷（m6 A）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，目前还没有关于m6 A修饰是否与ALV-J诱导的肿瘤形成有关的报道。本研究采用甲基化RNA免疫沉淀测序（MeRIP-seq）和RNA测序（RNA-seq）技术，系统地检测了正常肝脏和ALV-J诱导的肿瘤肝脏中m6 A甲基化和基因表达的差异，并进行了功能富集和共表达分析。结果鉴定出6,541个m6 A甲基化峰，主要富集在CDS中，超过83%的转录物含有1-2个m6 A峰。对于RNA-seq，分别鉴定出1，896个和1，757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，我们确定了17个lncRNA，通常存在于不同表达的甲基化组和转录组。通过共表达分析，最终鉴定出126个差异表达的lncRNA和18个可能与m6 A相关的甲基转移酶，表明m6 A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m6 A在ALV-J感染鸡肿瘤肝脏中的表达谱，为研究m6 A修饰在ALV-J诱导肿瘤发生中的作用提供了基础。本研究为ALV-J的表观遗传病因学和发病机制的研究提供了线索。
Avian Leukosis Virus Subgroup J (ALV-J) is a tumorigenic virus with high morbidity and rapid transmission. N6-methyladenosine (m6A) is a common epigenetic modification that may be closely related to the pathogenicity of ALV-J. Currently, there are no reports on whether m6A 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 m6A 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 m6A methylated peaks, mainly enriched in CDS, and more than 83% of the transcripts contained 1-2 m6A 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 m6A-related methyltransferases were finally identified and connected, suggesting that m6A 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 m6A expression profile in tumor livers induced by ALV-J infection in chickens, which provides a basis for studying the role of m6A modification in ALV-J induced tumorigenesis. This study provides clues for studying the epigenetic etiology and pathogenesis of ALV-J.