Transcriptome-wide dynamics of m6A methylation in tumor livers induced by ALV-J infection in chickens

Authors: ZHANG, XINHENG - South China Agricultural University; ZHAO, QIQI - South China Agricultural University; YAO, ZIQI - South China Agricultural University; CHEN, LIYI - South China Agricultural University; HE, YAYUAN - South China Agricultural University; XIE, ZI - South China Agricultural University; Zhang, Huanmin; LIN, WENCHENG - South China Agricultural University; CHEN, FENG - South China Agricultural University; XIE, QINGMEI - South China Agricultural University

Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/28/2022
Publication Date: 4/22/2022
Citation: Zhang, X., Zhao, Q., Yao, Z., Chen, L., He, Y., Xie, Z., Zhang, H., Lin, W., Chen, F., Xie, Q. 2022. Transcriptome-wide dynamics of m6A methylation in tumor livers induced by ALV-J infection in chickens. Journal of Immunology. 13. Article 868892. https://doi.org/10.3389/fimmu.2022.868892.
DOI: https://doi.org/10.3389/fimmu.2022.868892

Interpretive Summary: Avian Leukosis Virus Subgroup J (ALV-J) is a tumorigenic virus capable of inducing severe morbidity and rapid transmission in chicken and the current prevention approach is heavily depending on eradication measures. Although, the US poultry industry has been doing an outstanding job in preventing ALV-J infection and transmission, but it also economically costs the industry annually. Sporadic outbreaks have been reported in the rest of the world. Therefore, ALV-J continues to present a threat to the world poultry industry. This study examined the differences of DNA modification markers and non-coding expression data in both ALV-J tumor and normal chicken tissues. The findings of this study suggest that some of the DNA modification markers and the non-coding RNAs are involved in ALV-J induced tumor formation. This study may have paved the way for studying new genetic markers and advancing the basic understanding on ALV-J induced the diseases in poultry.

Technical Abstract: 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.