Kronja Iva, Yuan Bingbing, Eichhorn Stephen W, Dzeyk Kristina, Krijgsveld Jeroen, Bartel David P, Orr-Weaver Terry L
Whitehead Institute, Cambridge, MA 02142, USA.
Whitehead Institute, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Cell Rep. 2014 Jun 12;7(5):1495-1508. doi: 10.1016/j.celrep.2014.05.002. Epub 2014 May 29.
The oocyte-to-embryo transition marks the onset of development. The initial phase of this profound change from the differentiated oocyte to the totipotent embryo occurs in the absence of both transcription and mRNA degradation. Here we combine global polysome profiling, ribosome-footprint profiling, and quantitative mass spectrometry in a comprehensive approach to delineate the translational and proteomic changes that occur during this important transition in Drosophila. Our results show that PNG kinase is a critical regulator of the extensive changes in the translatome, acting uniquely at this developmental window. Analysis of the proteome in png mutants provided insights into the contributions of translation to changes in protein levels, revealing a compensatory dynamic between translation and protein turnover during proteome remodeling at the return to totipotency. The proteome changes additionally suggested regulators of meiosis and early embryogenesis, including the conserved H3K4 demethylase LID, which we demonstrated is required during this period despite transcriptional inactivity.
卵母细胞向胚胎的转变标志着发育的开始。从分化的卵母细胞到全能胚胎这一深刻变化的初始阶段发生在转录和mRNA降解均不存在的情况下。在这里,我们采用综合方法,结合全局多核糖体谱分析、核糖体足迹谱分析和定量质谱分析,来描绘果蝇这一重要转变过程中发生的翻译和蛋白质组变化。我们的结果表明,PNG激酶是翻译组广泛变化的关键调节因子,在这个发育窗口发挥独特作用。对png突变体蛋白质组的分析为翻译对蛋白质水平变化的贡献提供了见解,揭示了在恢复全能性的蛋白质组重塑过程中翻译与蛋白质周转之间的补偿动态。蛋白质组变化还提示了减数分裂和早期胚胎发育的调节因子,包括保守的H3K4去甲基化酶LID,我们证明在此期间尽管转录不活跃,但它是必需的。