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Age-related differences in the translational landscape of mammalian oocytes.
Aging Cell ( IF 7.8 ) Pub Date : 2020-09-20 , DOI: 10.1111/acel.13231
Edgar Del Llano 1, 2 , Tomas Masek 2 , Lenka Gahurova 1, 3 , Martin Pospisek 2 , Marketa Koncicka 1 , Anna Jindrova 1 , Denisa Jansova 1 , Rajan Iyyappan 1 , Kristina Roucova 2 , Alexander W Bruce 3 , Michal Kubelka 1 , Andrej Susor 1
Affiliation  

Increasing maternal age in mammals is associated with poorer oocyte quality, involving higher aneuploidy rates and decreased developmental competence. Prior to resumption of meiosis, fully developed mammalian oocytes become transcriptionally silent until the onset of zygotic genome activation. Therefore, meiotic progression and early embryogenesis are driven largely by translational utilization of previously synthesized mRNAs. We report that genome‐wide translatome profiling reveals considerable numbers of transcripts that are differentially translated in oocytes obtained from aged compared to young females. Additionally, we show that a number of aberrantly translated mRNAs in oocytes from aged females are associated with cell cycle. Indeed, we demonstrate that four specific maternal age‐related transcripts (Sgk1, Castor1, Aire and Eg5) with differential translation rates encode factors that are associated with the newly forming meiotic spindle. Moreover, we report substantial defects in chromosome alignment and cytokinesis in the oocytes of young females, in which candidate CASTOR1 and SGK1 protein levels or activity are experimentally altered. Our findings indicate that improper translation of specific proteins at the onset of meiosis contributes to increased chromosome segregation problems associated with female ageing.

中文翻译:

哺乳动物卵母细胞翻译景观中与年龄相关的差异。

哺乳动物中母亲年龄的增加与较差的卵母细胞质量有关,包括较高的非整倍体率和发育能力下降。在减数分裂恢复之前,完全发育的哺乳动物卵母细胞在转录上保持沉默,直到合子基因组激活开始。因此,减数分裂进程和早期胚胎发生在很大程度上是由先前合成的 mRNA 的翻译利用驱动的。我们报告说,全基因组翻译组分析显示,与年轻女性相比,从老年卵母细胞获得的卵母细胞中存在大量差异翻译的转录本。此外,我们发现老年女性卵母细胞中的一些异常翻译的 mRNA 与细胞周期有关。事实上,我们证明了四种特定的母亲年龄相关的转录本(Sgk1Castor1AireEg5 ) 具有不同的翻译率编码与新形成的减数分裂纺锤体相关的因子。此外,我们报告了年轻女性卵母细胞染色体排列和胞质分裂的重大缺陷,其中候选 CASTOR1 和 SGK1 蛋白水平或活性被实验改变。我们的研究结果表明,减数分裂开始时特定蛋白质的不当翻译会导致与女性衰老相关的染色体分离问题增加。
更新日期:2020-10-23
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