Transcriptome-wide N6-methyladenine methylation in granulosa cells of women with decreased ovarian reserve.
Transcriptome-wide N6-methyladenine methylation in granulosa cells of women with decreased ovarian reserve.
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卵巢储备功能下降的女性颗粒细胞中全转录组 N6-甲基腺嘌呤甲基化
DOI：
10.1186/s12864-022-08462-3
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发表时间：
2022-03-28
期刊：
影响因子：
4.4
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Liu C;Li L;Yang B;Zhao Y;Dong X;Zhu L;Ren X;Huang B;Yue J;Jin L;Zhang H;Wang L
出现的epitranscriptome在女性生育中起着至关重要的作用。N6-甲基腺嘌呤（m6 A）甲基化作为最常见的mRNA内部修饰，调控着mRNA的命运和翻译效率。然而，m6 A甲基化是否参与了衰老相关的卵巢储备下降尚未调查。在此，我们在年轻女性（年轻组）和老年女性（老年组）的卵巢颗粒细胞中进行了m6 A全转录组分析。m6 A甲基化分布在CDS和3 'UTR区域高度保守和富集。此外，在老年组中发现了更多的m6 A甲基化基因。生物信息学分析表明，m6 A甲基化基因在FoxO信号通路、粘附连接和肌动蛋白细胞骨架调控中富集。老年组中共有435个基因表达差异，其中58个基因被m6 A修饰。利用qRT-PCR技术验证了m6 A对BUB 1B、PHC 2、TOP 2A、DDR2、KLF 13和RYR 2等基因的表达调控，这些基因可能与卵巢衰老过程中卵巢功能的下降有关。因此，我们的发现揭示了m6 A修饰的转录意义，并提供了潜在的治疗靶点，以促进老年妇女的生育保留。在线版本包含补充材料，可通过10.1186/s12864-022-08462-3获得。
The emerging epitranscriptome plays an essential role in female fertility. As the most prevalent internal mRNA modification, N6-methyladenine (m6A) methylation regulate mRNA fate and translational efficiency. However, whether m6A methylation was involved in the aging-related ovarian reserve decline has not been investigated. Herein, we performed m6A transcriptome-wide profiling in the ovarian granulosa cells of younger women (younger group) and older women (older group). m6A methylation distribution was highly conserved and enriched in the CDS and 3’UTR region. Besides, an increased number of m6A methylated genes were identified in the older group. Bioinformatics analysis indicated that m6A methylated genes were enriched in the FoxO signaling pathway, adherens junction, and regulation of actin cytoskeleton. A total of 435 genes were differently expressed in the older group, moreover, 58 of them were modified by m6A. Several specific genes, including BUB1B, PHC2, TOP2A, DDR2, KLF13, and RYR2 which were differently expressed and modified by m6A, were validated using qRT-PCR and might be involved in the decreased ovarian functions in the aging ovary. Hence, our finding revealed the transcriptional significance of m6A modifications and provide potential therapeutic targets to promote fertility reservation for aging women. The online version contains supplementary material available at 10.1186/s12864-022-08462-3.
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影响因子：
14.9
作者：
Kanehisa M;Furumichi M;Sato Y;Ishiguro-Watanabe M;Tanabe M
通讯作者：
Tanabe M
影响因子：
5.5
作者：
Guo, Gangqiang;Shi, Xinyu;Xue, Xiangyang
通讯作者：
Xue, Xiangyang
影响因子：
4.3
作者：
Hu, Zhenhua;Cai, Mingbo;Guo, Ruixia
通讯作者：
Guo, Ruixia
影响因子：
6.1
作者：
Balakier, H;Dziak, E;Opas, M
通讯作者：
Opas, M
影响因子：
5.6
作者：
Ding, Chenyue;Zou, Qinyan;Huang, Boxian
通讯作者：
Huang, Boxian