Comprehensive profiling analysis of the N6-methyladenosine-modified circular RNA transcriptome in cultured cells infected with Marek\u2019s disease virus

Aijun Sun,Jun Luo,Guoqing Zhuang,Ying Liu,Man Teng,Shuaikang Yang,Luping Zheng,Rui Wang,Gaiping Zhang,Xiaojing Zhu

doi:10.1038/s41598-021-90548-1

Abstract

Marek’s disease virus (MDV) induces severe immunosuppression and lymphomagenesis in the chicken, its natural host, and results in a condition that investigated the pathogenesis of MDV and have begun to focus on the expression profiling of circular RNAs (circRNAs). However, little is known about how the expression of circRNAs is referred to as Marek’s disease. Previous reports have is regulated during MDV replication. Here, we carried out a comprehensive profiling analysis of N6-methyladenosine (m6A) modification on the circRNA transcriptome in infected and uninfected chicken embryonic fibroblast (CEF) cells. Methylated RNA immunoprecipitation sequencing (MeRIP-Seq) revealed that m6A modification was highly conserved in circRNAs. Comparing to the uninfected group, the number of peaks and conserved motifs were not significantly different in cells that were infected with MDV, although reduced abundance of circRNA m6A modifications. However, gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses revealed that the insulin signaling pathway was associated with the regulation of m6A modified circRNAs in MDV infection. This is the first report to describe alterations in the transcriptome-wide profiling of m6A modified circRNAs in MDV-infected CEF cells.

Highlights

Marek’s disease virus (MDV) causes a fatal disease that is referred to as Marek’s disease (MD)
GO enrichment analysis for biological processes (BP) indicated that genes related to chromosome segregation were up-regulated (Fig. 2B)
For molecular functions (MF), genes related to carbohydrate binding were up-regulated, while genes related to glycosaminoglycan binding were down-regulated (Fig. 2C)

Summary

Introduction

Marek’s disease virus (MDV) causes a fatal disease that is referred to as Marek’s disease (MD). 5′-Cap and 3′-poly(A) tail modifications can play an important role in the regulation of transcription, while the internal modification of messenger RNA (mRNA) is used to maintain stability. m6A is the most common reversible base modification on RNA and can affect transcription, splicing, localization, translation, structure stability, and the post-transcriptional regulation of gene expression. A variety of reading proteins have been identified by RNA pull-down assays, including YTH domain protein, nuclear heterogeneous ribosomal protein (hnRNP), and eukaryotic initiation factor (EIF). These reading proteins can bind to the m6A methylation region, weakening homologous binding to RNA-binding proteins and changing the secondary structure of the RNA to regulate interactions between protein and RNA15,21

Methods

Results

Discussion

Conclusion