Cui Wei, Pizzollo Jason, Han Zhengbin, Marcho Chelsea, Zhang Kun, Mager Jesse
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, Massachusetts.
Harbin Institute of Technology, School of Life Science and Technology, Harbin, China.
Mol Reprod Dev. 2016 Feb;83(2):124-31. doi: 10.1002/mrd.22600. Epub 2015 Dec 15.
Nucleolar protein 2 (NOP2) is evolutionarily conserved from yeast to human, and has been found to play an important role in accelerating cell proliferation, cell-cycle progression, and tumor aggressiveness. The expression pattern and function of Nop2 during early mammalian embryo development, however, has not been investigated. We identified Nop2 as an essential gene for development to the blastocyst stage while performing an RNA interference (RNAi)-based screen in mouse preimplantation embryos. Nop2 is expressed throughout preimplantation development, with highest mRNA and protein accumulation at the 8-cell and morula stages, respectively. RNAi-mediated knockdown of Nop2 results in embryos that arrest as morula. NOP2-deficient embryos exhibit reduced blastomere numbers, greatly increased apoptosis, and impaired cell-lineage specification. Furthermore, knockdown of Nop2 results in global reduction of all RNA species, including rRNA, small nuclear RNA, small nucleolar RNA, and mRNA. Taken together, our results demonstrate that Nop2 is an essential gene for blastocyst formation, and is required for RNA processing and/or stability in vivo during preimplantation embryo development in the mouse.
核仁蛋白2(NOP2)在从酵母到人类的进化过程中高度保守,并且已被发现对加速细胞增殖、细胞周期进程以及肿瘤侵袭性发挥重要作用。然而,Nop2在哺乳动物早期胚胎发育过程中的表达模式和功能尚未得到研究。在对小鼠植入前胚胎进行基于RNA干扰(RNAi)的筛选时,我们确定Nop2是发育至囊胚阶段所必需的基因。Nop2在整个植入前发育过程中均有表达,其mRNA和蛋白质分别在8细胞期和桑椹胚期积累最多。RNAi介导的Nop2敲低导致胚胎停滞在桑椹胚阶段。NOP2缺陷型胚胎的卵裂球数量减少,凋亡显著增加,细胞谱系分化受损。此外,Nop2的敲低导致包括rRNA、小核RNA、小核仁RNA和mRNA在内的所有RNA种类的整体减少。综上所述,我们的结果表明Nop2是囊胚形成所必需的基因,并且在小鼠植入前胚胎发育过程中对体内RNA加工和/或稳定性是必需的。