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Genes Environ
2021 Nov 06;431:49. doi: 10.1186/s41021-021-00223-0.
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Comprehensive analysis of differences of N6-methyladenosine of lncRNAs between atrazine-induced and normal Xenopus laevis testis.
Qi X, Geng X, Zhang J, Qu B, Zhang X, Jia Q, Yin W, Bo C, Liu Y, Li H, Sai L, Han M, Peng C.
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BACKGROUND: Increasing evidence suggested N6-methyladenosine (m6A) modification is crucial for male germline development. However, m6A modification of lncRNAs gains a little attention in amphibians in recent years. Xenopus laevis (X. laevis) was chosen to be an ideal model organism for testing environmental endocrine disrupting chemicals (EDCs) exposure and resultant effects. Atrazine (AZ) as an endocrine disrupt can effect development of testis in amphibians. Our previous study revealed that m6A is a highly conserved modification across the species.
RESULTS: The results of m6A sequences showed that m6A-methylated lncRNAs enriched in intergenic region in testes of X. laevis. We further examined the differential expression of lncRNAs m6A sites in testes of AZ-exposed and compared with that in animals from control group. The results indicated that up to 198 differentially methylated m6A sites were detected within 188 lncRNAs, in which 89 significantly up-methylated sites and 109 significantly down-methylated sites. Data from KEGG pathway analysis indicated that AZ-affected lncRNAs m6A sites were mainly involved in 10 pathways in which 3 mutual pathways were found in the result of differentially m6A-methylated mRNAs.
CONCLUSIONS: These findings suggested that differentially m6A-methylated lncRNAs and these 3 pathways may act on regulatory roles in abnormal testis development of AZ-exposed X. laevis. This study for the first time provides insights into the profile of lncRNAs m6A modifications in amphibian species.
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34742356 ???displayArticle.pmcLink???PMC8572474 ???displayArticle.link???Genes Environ ???displayArticle.grants???[+]
202012010629 health commission of shandong province, 202019162 ji'nan science and technology bureau, 81573198 national natural science foundation of china, 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 lncRNAs in AZ-exposed and control groups
Fig. 2. Overview the distribution positions of m6A-methylated lncRNAs in the testes of X. laevis from control and AZ-exposed groups. a: Pie charts showing the percentage of the distribution positions of m6A-methylated lncRNAs relatived to its mRNA in control group. b: Pie charts showing the percentage of the distribution positions of m6A-methylated lncRNAs in AZ-exposed group. c: Distributions of mean fold enrichment of m6A-methylated lncRNAs in six segments in control group. d: Distributions of mean fold enrichment of m6A-methylated lncRNAs in six segments in AZ-exposed group. Error bars represent the standard error of the mean. The mean fold enrichment in the intergenic segments was the largest both in the control and AZ-exposed group with lower standard error of the mean
Fig. 3. Distribution of differentially methylated m6A sites of lncRNAs. a: Pie charts showing the percentage of up-methylated m6A peaks in six segments. b: Pie charts showing the percentage of down-methylated m6A peaks in six segments. c: Statistics of meanof the distribution positions of m6A-methylated lncRNAs in six segments with up- and down-methylated sites. Error bars represent the standard error of the mean
Fig. 4. The annotated significant pathways targeted by the enrichment score of the differentially m6A-methylated (up-methylated (a) and down-methylated (b)) lncRNAs-related genes in testis of X. laevis exposed to 100 μg/L AZ. The horizontal axis is the -LogP (logarithm of P-value) for the pathway and the vertical axis is the pathway category
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