Mak Winifred, Xia Jing, Cheng Ee-Chun, Lowther Katie, Lin Haifan
3Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06519 USA.
Women's Health Department, Dell Medical School, Medical Park Tower, 1301 W. 38th Street, Suite 705, Austin, TX 78705 USA.
Cell Biosci. 2018 Oct 19;8:54. doi: 10.1186/s13578-018-0251-1. eCollection 2018.
RNA binding proteins play a pivotal role during the oocyte-to-embryo transition and maternal phase of embryogenesis in invertebrates, but their function in these processes in mammalian systems remain largely understudied.
Here we report that a member of the Pumilio/FBF family of RNA binding proteins in mice, Pumilio 1 (1), is a maternal effect gene. The absence of maternal PUM1 in the oocyte does not affect meiotic maturation but leads to abnormal preimplantation development. Furthermore, genome-wide transcriptome analysis of oocytes and embryos revealed that there is a concomitant perturbation of the mRNA milieu. Of note, putative PUM1 mRNA targets were equally perturbed as non-direct targets, which indicates that PUM1 regulates the stability of maternal mRNAs both directly and indirectly. We show a known PUM1 target essential for meiosis and preimplantation development, is not degraded appropriately during meiosis, leading to an increase in CDK1 protein in mature oocytes, which indicates that PUM1 post-transcriptionally regulates mRNA; this could partially explain the observed abnormal preimplantation development. Furthermore, our results show that maternal and zygotic PUM1 are required for postnatal survival.
These findings indicate that PUM1 is essential in the process of cytoplasmic maturation and developmental competence of the oocyte. These results reveal an important function of maternal PUM1 as a post-transcriptional regulator during mammalian embryogenesis.
RNA结合蛋白在无脊椎动物的卵母细胞向胚胎转变以及胚胎发生的母源阶段发挥着关键作用，但它们在哺乳动物系统这些过程中的功能仍 largely 未被充分研究。
在此我们报告，小鼠中RNA结合蛋白Pumilio/FBF家族的一个成员Pumilio 1（PUM1）是一个母源效应基因。卵母细胞中母源PUM1的缺失不影响减数分裂成熟，但会导致植入前发育异常。此外，对卵母细胞和胚胎的全基因组转录组分析表明，mRNA环境存在伴随的扰动。值得注意的是，假定的PUM1 mRNA靶标与非直接靶标同样受到扰动，这表明PUM1直接和间接调节母源mRNA的稳定性。我们显示，一个对减数分裂和植入前发育至关重要的已知PUM1靶标，在减数分裂期间未被适当降解，导致成熟卵母细胞中CDK1蛋白增加，这表明PUM1在转录后调节mRNA；这可以部分解释观察到的植入前发育异常。此外，我们的结果表明，母源和合子PUM1是出生后存活所必需的。
这些发现表明PUM1在卵母细胞的细胞质成熟和发育能力过程中至关重要。这些结果揭示了母源PUM1在哺乳动物胚胎发生过程中作为转录后调节因子的重要功能。
