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Transcriptome-wide N6-methyladenosine modification profiling of long non-coding RNAs and circular RNA during growth of Marek’s disease virus in vitro

ABSTRACT: we profiled the transcriptome-wide m6A modification in lncRNAs and circRNA in MDV-infected chicken embryo fibroblast (CEF) cells. Methylated RNA immunoprecipitation sequencing results revealed that the lncRNA m6A modification is highly conserved with MDV infection increasing the expression of lncRNA m6A modified sites compared to uninfected cell controls. m6A modification was highly conserved in circRNAs. Comparing to the uninfected group, the number of peaks, conserved motifs, and abundance of circRNA m6A modification, was not significantly different in cells that were infected with MDV. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis revealed that lncRNA m6A modifications were highly associated with signaling pathways associated with MDV infection. The alterations seen in transcriptome-wide m6A occurring in lncRNAs following MDV-infection suggest this process plays important regulatory roles during MDV replication. And the insulin signaling pathway was associated with the regulation of m6A modified circRNAs in MDV infection. In summary, we report for the first time profiling of the alterations in transcriptome-wide m6A modification in lncRNAs and circRNA of MDV-infected CEF cells.

ORGANISM(S): Gallus gallus

PROVIDER: GSE166240 | GEO | 2021/04/28

REPOSITORIES: GEO

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Project description:Purpose: Marek's disease virus (MDV) is an oncogenic herpesvirus that can induce T-cell lymphoma. Long noncoding RNA (lncRNA) strongly associated with various cancers and many other diseases. In chickens, lncRNAs have not been comprehensively identified. Here, we profiled mRNA and lncRNA repertoires in three groups of spleens from MDV-infected and non-infected chickens, including seven tumorous spleens (TS) from MDV-infected chickens, five spleens from the survivors (SS) without any lesion after MDV infection, and five noninfected spleens (NS) from chickens, to explore the underlying mechanism of host resistance to Marek's disease (MD). Results: By using precise lncRNA identification pipeline, we identified 1315 putative lncRNAs and 1166 known lncRNAs in spleen tissue. Genomic features of putative lncRNAs were characterized. Differentially expressed mRNAs, putative lncRNAs and known lncRNAs were profiled. Some previously reported MD resistance candidate genes, such as CTLA4, HDAC9 and CD72, were also found in our differentially expressed genes list. Moreover, we found that several intergroup specifically deregulated genes were involved in important biological processes and pathways, including B cell activation and Wnt signaling pathway. We conducted co-expression network using WGCNA and identified several hub genes that may play pivotal roles in MD resistance and tumorigenesis, e.g. CTLA4, SWAP70, CXCL12 and JCHAIN. According to the expression relationship between lncRNAs and MD resistance candidate mRNAs, five deregulated lncRNAs may implicate the chicken immunity by directly or indirectly regulating those hub genes. Conclusions: We profiled both lncRNA and mRNA expression patterns in MDV-infected chicken spleens. Expression variations of intergroup specifically deregulated genes engaged in important immune process likely contributed to robust immune system in the survivors. Some oncogenesis or MD resistance related genes deregulated between groups, like CTLA4, HDAC9 and CD72 were found. Co-expression network analysis manifested that lncRNAs may affect MD resistance and tumorigenesis in chicken spleens through their impact on expression of CTLA4, SWAP70 and some other genes that are critical in many important biological processes, such as B lymphocyte proliferation and activation.

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Transcriptome-wide N6-methyladenosine modification profiling of long non-coding RNAs and circular RNA during growth of Marek’s disease virus in vitro

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