Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Biol Reprod. 2022 Sep 12;107(3):723-731. doi: 10.1093/biolre/ioac098.
PETER PAN (PPAN), located to nucleoli and mitochondria, is a member of the Brix domain protein family, involved in rRNA processing through its rRNA binding motif and mitochondrial apoptosis by protecting mitochondria structure and suppressing basal autophagic flux. Ppan is important for cell proliferation and viability, and mutation of Ppan in Drosophila caused larval lethality and oogenesis failure. Yet, its role in mammalian reproduction remains unclear. In this study, we explored the function of Ppan in oocyte maturation and early embryogenesis using conditional knockout mouse model. Deficiency of maternal Ppan significantly downregulated the expression level of 5.8S rRNA, 18S rRNA, and 28S rRNA, though it had no effect on oocyte maturation or preimplantation embryo development. However, depletion of both maternal and zygotic Ppan blocked embryonic development at morula stage. Similar phenotype was obtained when only zygotic Ppan was depleted. We further identified no DNA binding activity of PPAN in mouse embryonic stem cells, and depletion of Ppan had minimum impact on transcriptome but decreased expression of 5.8S rRNA, 18S rRNA, and 28S rRNA nevertheless. Our findings demonstrate that Ppan is indispensable for early embryogenesis in mice.
彼得潘（PPAN）位于核仁与线粒体，是 Brix 结构域蛋白家族的成员，通过其 rRNA 结合基序参与 rRNA 加工，并通过保护线粒体结构和抑制基础自噬流来参与线粒体凋亡。Ppan 对细胞增殖和活力很重要，果蝇中 Ppan 的突变导致幼虫致死和卵子发生失败。然而，其在哺乳动物生殖中的作用尚不清楚。在这项研究中，我们使用条件敲除小鼠模型探索了 Ppan 在卵母细胞成熟和早期胚胎发生中的功能。母源 Ppan 的缺失显著下调了 5.8S rRNA、18S rRNA 和 28S rRNA 的表达水平，尽管它对卵母细胞成熟或着床前胚胎发育没有影响。然而，母源和合子源 Ppan 的缺失均阻断了胚胎发育至桑葚胚阶段。仅缺失合子源 Ppan 时也获得了相似的表型。我们进一步发现 PPAN 在小鼠胚胎干细胞中没有 DNA 结合活性，并且 Ppan 的缺失对转录组的影响最小，但 5.8S rRNA、18S rRNA 和 28S rRNA 的表达水平仍然降低。我们的研究结果表明，Ppan 对小鼠早期胚胎发生是不可或缺的。
