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首页> 外文期刊>Aging cell. >Integrative proteome analysis implicates aberrant RNA splicing in impaired developmental potential of aged mouse oocytes
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Integrative proteome analysis implicates aberrant RNA splicing in impaired developmental potential of aged mouse oocytes

机译：一致性蛋白质组分析意味着老年小鼠卵母细胞的发育潜力受损的异常RNA剪接

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Aging has many effects on the female reproductive system, among which decreased oocyte quality and impaired embryo developmental potential are the most important factors affecting female fertility. However, the mechanisms underlying oocyte aging are not yet fully understood. Here, we selected normal reproductively aging female mice and constructed a protein expression profile of metaphase II (MII) oocytes from three age groups. A total of 187 differentially expressed (DE) proteins were identified, and bioinformatics analyses showed that these DE proteins were highly enriched in RNA splicing. Next, RNA-seq was performed on 2-cell embryos from these three age groups, and splicing analysis showed that a large number of splicing events and genes were discovered at this stage. Differentially spliced genes (DSGs) in the two reproductively aging groups versus the younger group were enriched in biological processes related to DNA damage repair/response. Binding motif analysis suggested that PUF60?might be one of the core splicing factors causing a decline in DNA repair capacity in the subsequent development of oocytes from reproductively aging mice, and changing the splicing pattern of its potential downstream DSG Cdk9 could partially mimic phenotypes in the reproductively aging groups. Taken together, our study suggested that the abnormal expression of splicing regulation proteins in aged MII oocytes would affect the splicing of nascent RNA after zygotic genome activation in 2-cell embryos, leading to the production of abnormally spliced transcripts of some key genes associated with DNA damage repair/response, thus affecting the developmental potential of aged oocytes.
机译：老化对女性生殖系统具有许多影响，其中卵母细胞质量下降，胚胎发育潜力受损是影响女性生育的最重要因素。然而，卵母细胞老化的机制尚未完全理解。在这里，我们选择正常的生殖老化女性小鼠并构建了来自三岁基团的中期II（MII）卵母细胞的蛋白质表达谱。鉴定了总共187种差异表达（DE）蛋白质，并且生物信息学分析表明这些DE蛋白质在RNA剪接中高度富集。接下来，从这三个年龄组对2细胞胚胎进行RNA-SEQ，并且剪接分析表明在该阶段发现了大量剪接事件和基因。两种生殖老化基团中的差异剪接基因（DSG）与较年轻的群体富集在与DNA损伤修复/反应有关的生物学过程中。结合的基序分析表明PUF60？可能是核心剪接因子中的一种核心剪接因子之一，导致DNA修复能力下降到从生殖老化小鼠的卵母细胞的卵母细胞的发育中，并改变其潜在下游DSG CDK9的剪接模式可以部分模仿表型生殖老化团体。我们的研究表明，老年人MII卵母细胞中剪接调节蛋白的异常表达会影响在2细胞胚胎中的引程基因组活化后的新生RNA的剪接，导致产生与DNA相关的一些关键基因的异常剪接转录物损伤修复/响应，从而影响老年卵母细胞的发育潜力。

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