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Genes Environ
2023 Sep 01;451:23. doi: 10.1186/s41021-023-00279-0.
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M6A transcriptome-wide map of circRNAs identified in the testis of normal and AZ-treated Xenopus laevis.
Zhang X
,
Sai L
,
Zhang W
,
Kan X
,
Jia Q
,
Bo C
,
Yin W
,
Shao H
,
Han M
,
Peng C
.
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BACKGROUND: Evidence showed that N6-methyladenosine (m6A) is strongly associated with male germline development. However, the role of m6A methylation on circRNAs in amphibians remains unknown. In this study, we conducted m6A sequencing analysis to explore the m6A transcriptome-wide profile of circRNAs in testis tissues of Xenopus laevis (X. laevis) with and without treatment with 100 µg/L atrazine (AZ).
RESULTS: The analysis showed that m6A modification of circRNAs enriched in sense overlapping in testes of X. laevis. We identified the differential m6A modification sites within circRNAs in testes of AZ-exposed X. laevis and compared that with animals from control group. The results showed that a total of 1507 methylated m6A sites was induced by AZ (760 up-methylated and 747 down-methylated). The cross-analysis exhibited a negative correlation of differentially methylated m6A peaks and circRNAs expression level. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that 20 key pathways may be involved in the mechanism of testis damage of AZ-exposed X. laevis.
CONCLUSIONS: These findings indicated that differentially m6A-methylated circRNAs may play important roles in abnormal testis development of AZ-exposed X. laevis. This study is the first report about a map of m6A modification of circRNAs in male X. laevis and provides a basis for further studying on the function and mechanism of m6A methylation of circRNAs in the testis development of amphibian.
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37658417
???displayArticle.pmcLink???PMC10472591 ???displayArticle.link???Genes Environ ???displayArticle.grants???[+]
202012010629; 202112010222; M-20222055 Health Commission of Shandong Province, 202019108; 202019109 Ji'nan Science and Technology Bureau, 81573198; 30901214 National Natural Science Foundation of China, 2019QL001 the Innovation Project of Shandong Academy of Medical Sciences, Academic Promotion Programme of Shandong First Medical University, 2018ZX09711001-011 Ministry of Science and Technology of PRC
Fig. 1
Venn diagram showing the overlap of m6A peaks within circRNAs in the testes of control and AZ-exposed X. laevis
Fig. 2
Distribution of m6A-methylated circRNAs in the testes of control and AZ-exposed X. laevis a: Pie charts showing the percentage of the distribution positions of m6A-methylated circRNAs in control group. b: Pie charts showing the percentage of the distribution positions of m6A-methylated circRNAs in AZ-exposed group
Fig. 3
Volcano plots showing –log10 (P_value) versus log2FC in m6A methylated sites on circRNAs in the testes of control and AZ-exposed X. laevis. Red circles denote significantly up-regulated m6A methylated sites, whereas blue circles denote significantly down-regulated m6A methylated sites (p < 0.05 and fold change ≥ 4)
Fig. 4
Overview the distribution of differentially m6A modification sites of circRNAs. a: Pie charts showing the percentage of up-methylated m6A in five segments. b: Pie charts showing the percentage of down-methylated m6A peaks in five segments
Fig. 5
a: Dot plot of log2FC (circRNAs expression) against log2FC (differential m6A methylation) showing a negative correlation between overall m6A methylation and mRNA expression level (P = 0.02; Pearson R = -0.25). b: Four quadrant plots showing gene expression with differentially methylated m6A peaks
Fig. 6
The annotated significant pathways targeted by the enrichment score of the differentially m6A-methylated circRNAs-related genes including up-methylated (a) and down-methylated (b) in testis of X. laevis exposed to 100 µg/L AZ. The horizontal axis is the -log10 (P-value) for the pathway and the vertical axis is the pathway category
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