Liu Yingxiang, Feng Peiwen, Wei Xing, Xu Hongyu, Yu Mengying, Zhang Lei, Hao Weijie, Guo Zekun
Department of Orthopedic Surgery, Orthopedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, P.R. China.
Cell Commun Signal. 2024 Dec 18;22(1):604. doi: 10.1186/s12964-024-01976-1.
Timely and accurate translation of maternal mRNA is essential for oocyte maturation and early embryonic development. Previous studies have highlighted the importance of Primordial Germ cell 7 (PGC7) as a maternal factor in maintaining DNA methylation of maternally imprinted loci in zygotes. However, it is still unknown whether PGC7 is involved in the regulation of Maternal mRNA Translation. In this study, we have identified that PGC7-AKT1-YBX1 axis is involved in promoting the translation of maternal mRNAs. PGC7 not only sustains AKT1 activity by counteracting PP2A dephosphorylation and facilitating PDK1-AKT1 binding but also assists AKT1 in phosphorylating the translation inhibitor YBX1. In the absence of PGC7, despite increased PIK3CA expression and AKT1 phosphorylation, AKT1 is unable to phosphorylate YBX1. PGC7 facilitates the interaction between AKT1 and YBX1, enhancing YBX1-Serine 100 phosphorylation, which leads to YBX1 dissociation from eIF4E, thereby activating the translation of maternal Cyclin B1 and YAP1. The findings demonstrate the indispensability of PGC7 for translation activation in mammalian oocytes and provide a potential network regulated by PGC7 in early oogenesis.
母体mRNA的及时准确翻译对于卵母细胞成熟和早期胚胎发育至关重要。先前的研究强调了原始生殖细胞7（PGC7）作为母体因子在维持合子中母源印记位点DNA甲基化方面的重要性。然而，PGC7是否参与母体mRNA翻译的调控仍不清楚。在本研究中，我们发现PGC7-AKT1-YBX1轴参与促进母体mRNA的翻译。PGC7不仅通过对抗PP2A去磷酸化并促进PDK1-AKT1结合来维持AKT1活性，还协助AKT1磷酸化翻译抑制剂YBX1。在缺乏PGC7的情况下，尽管PIK3CA表达增加且AKT1磷酸化，但AKT1无法磷酸化YBX1。PGC7促进AKT1与YBX1之间的相互作用，增强YBX1丝氨酸100的磷酸化，导致YBX1从eIF4E解离，从而激活母体细胞周期蛋白B1和YAP1的翻译。这些发现证明了PGC7在哺乳动物卵母细胞翻译激活中的不可或缺性，并提供了PGC7在早期卵子发生中调控的潜在网络。
