Ming Hao, Iyyappan Rajan, Kakavand Kianoush, Dvoran Michal, Susor Andrej, Jiang Zongliang
Department of Animal Sciences, Genetics Institute, University of Florida, Gainesville, FL 32610, USA.
Laboratory of Biochemistry and Molecular Biology of Germ Cells, Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, Rumburska 89, 277 21 Libechov, Czech Republic.
bioRxiv. 2024 Oct 28:2024.10.28.620693. doi: 10.1101/2024.10.28.620693.
Translational regulation is pivotal during preimplantation development. However, how mRNAs are selected for temporal regulation and their dynamic utilization and fate during this period are still unknown. Using a high-resolution ribosome profiling approach, we analyzed the transcriptome, as well as monosome- and polysome-bound RNAs of mouse oocytes and embryos, defining an unprecedented extent of spatiotemporal translational landscapes during this rapid developmental phase. We observed previously unknown mechanisms of translational selectivity, i.e., stage-wise deferral of loading monosome-bound mRNAs to polysome for active translation, continuous translation of both monosome and polysome-bound mRNAs at the same developmental stage, and priming to monosomes after initial activation. We showed that a eukaryotic initiation factor Eif1ad3, which is exclusively translated in the 2-Cell embryo, is required for ribosome biogenesis post embryonic genome activation. Our study thus provides genome-wide datasets and analyses of spatiotemporal translational dynamics accompanying mammalian germ cell and embryonic development and reveals the contribution of a novel translation initiation factor to mammalian pre-implantation development.
翻译调控在着床前发育过程中至关重要。然而,在此期间,mRNA是如何被选择进行时间调控的,以及它们在此期间的动态利用和命运仍然未知。我们使用高分辨率核糖体谱分析方法,分析了小鼠卵母细胞和胚胎的转录组以及与单体核糖体和多聚核糖体结合的RNA,确定了在这个快速发育阶段前所未有的时空翻译图谱范围。我们观察到了以前未知的翻译选择性机制,即阶段特异性地将与单体核糖体结合的mRNA延迟加载到多聚核糖体上进行活跃翻译,在同一发育阶段与单体核糖体和多聚核糖体结合的mRNA都持续翻译,以及在初始激活后向单体核糖体的启动。我们发现,一种仅在二细胞胚胎中翻译的真核起始因子Eif1ad3,是胚胎基因组激活后核糖体生物发生所必需的。因此,我们的研究提供了全基因组数据集,并分析了伴随哺乳动物生殖细胞和胚胎发育的时空翻译动力学,揭示了一种新型翻译起始因子对哺乳动物着床前发育的贡献。