Miao Liyun, Yuan Yue, Cheng Feng, Fang Junshun, Zhou Fang, Ma Weirui, Jiang Yan, Huang Xiahe, Wang Yingchun, Shan Lingjuan, Chen Dahua, Zhang Jian
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
University of Chinese Academy of Sciences, Beijing 100101, China.
Development. 2017 Jan 1;144(1):128-138. doi: 10.1242/dev.144642. Epub 2016 Dec 2.
A large amount of maternal RNA is deposited in oocytes and is reserved for later development. Control of maternal RNA translation during oocyte maturation has been extensively investigated and its regulatory mechanisms are well documented. However, translational regulation of maternal RNA in early oogenesis is largely unexplored. In this study, we generated zebrafish zar1 mutants that result in early oocyte apoptosis and fully penetrant male development. Loss of p53 suppresses the apoptosis in zar1 mutants and restores oocyte development. zar1 immature ovaries show upregulation of proteins implicated in endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). More importantly, loss of Zar1 causes marked upregulation of zona pellucida (ZP) family proteins, while overexpression of ZP proteins in oocytes causes upregulation of stress-related activating transcription factor 3 (atf3), arguing that tightly controlled translation of ZP proteins is essential for ER homeostasis during early oogenesis. Furthermore, Zar1 binds to ZP gene mRNAs and represses their translation. Together, our results indicate that regulation of translational repression and de-repression are essential for precisely controlling protein expression during early oogenesis.
大量母体RNA沉积在卵母细胞中，留待后期发育使用。卵母细胞成熟过程中母体RNA翻译的调控已得到广泛研究，其调控机制也有充分记载。然而，早期卵子发生过程中母体RNA的翻译调控在很大程度上仍未被探索。在本研究中，我们生成了斑马鱼zar1突变体，该突变体导致早期卵母细胞凋亡并完全表现为雄性发育。p53缺失可抑制zar1突变体中的细胞凋亡并恢复卵母细胞发育。zar1未成熟卵巢显示出与内质网（ER）应激和未折叠蛋白反应（UPR）相关的蛋白质上调。更重要的是，Zar1缺失导致透明带（ZP）家族蛋白显著上调，而在卵母细胞中过表达ZP蛋白会导致应激相关的激活转录因子3（atf3）上调，这表明在早期卵子发生过程中严格控制ZP蛋白的翻译对于内质网稳态至关重要。此外，Zar1与ZP基因mRNA结合并抑制其翻译。总之，我们的结果表明，翻译抑制和去抑制的调控对于在早期卵子发生过程中精确控制蛋白质表达至关重要。
