RNA-Binding Protein IGF2BP2/IMP2 is a Critical Maternal Activator in Early Zygotic Genome Activation
RNA-Binding Protein IGF2BP2/IMP2 is a Critical Maternal Activator in Early Zygotic Genome Activation
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RNA 结合蛋白 IGF2BP2/IMP2 是早期合子基因组激活的关键母体激活剂
DOI：
10.1002/advs.201900295
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发表时间：
2019-08-07
期刊：
影响因子：
15.1
通讯作者：
Chen, Zi-Jiang
中科院分区：
文献类型：
--
作者：
Liu, Hong-Bin;Muhammad, Tahir;Chen, Zi-Jiang
许多参与合子基因组激活（ZGA）的基因已被确定，但与小鼠ZGA直接相关的RNA结合母体因子仍不清楚。目前的研究表明，母体缺失Igf 2bp 2（通常也称为Imp 2）在小鼠胚胎中导致早期胚胎发育停滞在体外2细胞阶段。小鼠2细胞期胚胎的转录组学和蛋白质组学分析表明，IMP 2的缺失下调了Ccar 1和Rps 14的表达，这两者都是早期胚胎发育能力所必需的。IGF 2是IMP 2的靶点，当添加到培养基中时，可增加成功发育至囊胚期的野生型胚胎的比例：从未处理对照组的29%增加至65%（50 × 10（-9）M IGF 2）。此外，在一项与胚胎移植相关的实验中，接受IGF 2处理的胚胎的养母比接受未经处理的对照胚胎的雌性每只雌性产下更多的幼崽。在临床来源的人卵母细胞中，向培养基中添加IGF 2显著提高了成功发育的胚胎的比例。总的来说，研究结果表明，IMP 2是必不可少的调控和激活基因已知参与ZGA和揭示潜在的胚胎发育相关的效用IGF 2的动物生物技术和人类辅助生殖。
A number of genes involved in zygotic genome activation (ZGA) have been identified, but the RNA-binding maternal factors that are directly related to ZGA in mice remain unclear. The present study shows that maternal deletion of Igf2bp2 (also commonly known as Imp2) in mouse embryos causes early embryonic developmental arrest in vitro at the 2-cell-stage. Transcriptomics and proteomics analyses of 2-cell-stage embryos in mice reveal that deletion of IMP2 downregulates the expression of Ccar1 and Rps14, both of which are required for early embryonic developmental competence. IGF2, a target of IMP2, when added in culture media, increases the proportion of wild-type embryos that develop successfully to the blastocyst stage: from 29% in untreated controls to 65% (50 x 10(-9) M IGF2). Furthermore, in an experiment related to embryo transfer, foster mothers receiving IGF2-treated embryos deliver more pups per female than females who receive untreated control embryos. In clinically derived human oocytes, the addition of IGF2 to the culture media significantly enhances the proportion of embryos that develop successfully. Collectively, the findings demonstrate that IMP2 is essential for the regulation and activation of genes known to be involved in ZGA and reveal the potential embryonic development-related utility of IGF2 for animal biotechnology and for assisted reproduction in humans.