Genome-wide identification m6A modified circRNAs revealed their key roles in skin ulceration syndrome disease development in Apostichopus japonicus. Issue 127 (August 2022)

• Record Type: Journal Article
• Authors: Duan, Xuemei; Shao, Yina; Che, Zhongjie; Zhao, Xuelin; Guo, Ming; Li, Chenghua; Liang, Weikang
• Is Part Of: Fish & shellfish immunology. Issue 127(2022)
• Page Start: 748
• Page End: 757
• Publication Date: 2022-08
• Subjects: Apostichopus japonicus -- m6A circRNA -- Skin ulceration syndrome -- Disease-resistant; Fishes -- Immunology -- Periodicals; Shellfish -- Immunology -- Periodicals; Poissons -- Immunologie -- Périodiques; Crustacés -- Immunologie -- Périodiques; 571.9617
• DOI: 10.1016/j.fsi.2022.07.008
• Languages: English
• ISSNs: 1050-4648

Abstract

Abstract: Circular RNAs (circRNAs) are novel endogenous non-coding RNAs (ncRNAs) and can be acted as competing endogenous RNAs (ceRNAs) to regulate microRNA (miRNA) and downstream gene expression. Recently, m 6 A modification has been found in circRNA, and m 6 A circRNAs also play important roles in various biological processes and a variety of diseases. Our previous study had been demonstrated that circRNAs were differentially expressed in skin ulceration syndrome (SUS) diseased sea cucumber Apostichopus japonicus . However, whether the function of circRNAs are dependent on m 6 A levels are largely unknown. Here, we firstly investigated the genome-wide map of m 6 A circRNAs in sea cucumbers with different stages of Vibrio splendidus challenge, that's Control group, SUS-diseased group, and SUS-resistant group. MeRIP-seq revealed that m 6 A abundances were enriched in circRNAs in all three groups, especially for SUS-resistant group. Among them, more than 62% of modified circRNAs harbor only a single m 6 A peak and about 55% of m 6 A sites in circRNAs were derived from sense overlapping in each group. After V. splendidus infection, we found that most of m 6 A peaks in circRNAs were upregulated and less were downregulated in both SUS-diseased and SUS-resistant groups when compared with Control. Furthermore, GO analysis indicated that the host genes of circRNAs with dysregulated m 6 A peaks in SUS-diseased and SUS-resistant groups were both mainly enriched in the adhesion pathway. More importantly, we discovered that more than 50% m 6 A circRNAs showed a positive correlation between the circRNAs expression and m 6 A methylation levels both in SUS-diseased and SUS-resistant groups. Therefore, a core circRNA-miRNA-mRNA (ceRNA) network whether influenced by m 6 A modification was constructed based on conjoint analysis. Our results indicated that several selected m 6 A circRNAs bind with miRNAs were mainly targeting to ubiquitylation system and adhesion pathway. What's more, three candidate m 6 A circRNAs and three target genes were validated by MeRIP-qPCR and qPCR, whose m 6 A levels in circRNA and mRNA expressions were consistent with disease occurrence or disease resistance. All of our current findings suggested that m 6 A circRNAs could play important roles during pathogen infection and might be served as a new molecular biomarker in SUS disease diagnose of A. japonicus . Highlights: The genome-wide map of m 6 A circRNAs profiles was sequenced in sea cucumbers. More than 62% of modified circRNAs harbor only a single m6A peak. V. splendidus challenge upregulated most of m 6 A peaks in circRNAs in both SUS-diseased and SUS-resistant groups. GO analysis indicated circRNAs with dysregulated m 6 A peaks were both mainly enriched in the adhesion pathway. More than 50% m 6 A circRNAs showed a positive correlation between the circRNAs expression and m 6 A methylation levels.