ZAR1 and ZAR2 are required for oocyte meiotic maturation by regulating the maternal transcriptome and mRNA translational activation
ZAR1 and ZAR2 are required for oocyte meiotic maturation by regulating the maternal transcriptome and mRNA translational activation
复制标题
ZAR1 和 ZAR2 通过调节母体转录组和 mRNA 翻译激活，是卵母细胞减数分裂成熟所必需的
DOI：
10.1093/nar/gkz863
复制
发表时间：
2019-12-02
影响因子：
14.9
通讯作者：
Fan, Heng-Yu
中科院分区：
文献类型：
--
作者：
Rong, Yan;Ji, Shu-Yan;Fan, Heng-Yu
摘要Zar1是最早被发现的哺乳动物母系效应基因之一。来自zar1缺失的雌性小鼠的胚胎在合子基因组激活之前被阻断；然而，其潜在机制尚不清楚。通过敲除小鼠体内的Zar1及其同系物Zar2，我们揭示了这些基因在卵母细胞减数分裂成熟中的新功能。zar1 /2缺失的卵母细胞表现出减数分裂恢复和极体-1发射延迟，减数分裂纺锤体形成异常和染色体非整倍体的发生率更高。zar1 /2缺失小鼠的卵母细胞含有许多母体mrna水平降低，蛋白质合成水平降低。在zar1 /2缺失的卵母细胞中，关键的成熟相关变化未能发生，包括编码细胞周期蛋白cyclin B1和WEE2的母体mrna的翻译激活，以及母体到合子转化（MZT）许可因子BTG4。结果母体mRNA衰变受损，MZT被消除。ZAR1/2结合mrna调节其3 ' - utr的翻译活性，并与其他卵母细胞蛋白相互作用，包括mrna稳定蛋白MSY2和细胞质晶格组分。这些结果反驳了ZAR1仅在受精后起作用的传统观点，并突出了ZAR1/2在成熟卵母细胞中调节母体转录组和翻译激活的先前未被认识到的作用。
Abstract Zar1 was one of the earliest mammalian maternal-effect genes to be identified. Embryos derived from Zar1-null female mice are blocked before zygotic genome activation; however, the underlying mechanism remains unclear. By knocking out Zar1 and its homolog Zar2 in mice, we revealed a novel function of these genes in oocyte meiotic maturation. Zar1/2-deleted oocytes displayed delayed meiotic resumption and polar body-1 emission and a higher incidence of abnormal meiotic spindle formation and chromosome aneuploidy. The grown oocytes of Zar1/2-null mice contained decreased levels of many maternal mRNAs and displayed a reduced level of protein synthesis. Key maturation-associated changes failed to occur in the Zar1/2-null oocytes, including the translational activation of maternal mRNAs encoding the cell-cycle proteins cyclin B1 and WEE2, as well as maternal-to-zygotic transition (MZT) licensing factor BTG4. Consequently, maternal mRNA decay was impaired and MZT was abolished. ZAR1/2 bound mRNAs to regulate the translational activity of their 3′-UTRs and interacted with other oocyte proteins, including mRNA-stabilizing protein MSY2 and cytoplasmic lattice components. These results countered the traditional view that ZAR1 only functions after fertilization and highlight a previously unrecognized role of ZAR1/2 in regulating the maternal transcriptome and translational activation in maturing oocytes.