关键词: MZT MicroRNA SLAM-seq ZGA

Mesh : Animals Zebrafish / metabolism RNA, Messenger / genetics metabolism Zygote / metabolism Embryonic Development / genetics MicroRNAs / genetics metabolism Gene Expression Regulation, Developmental

来  源:   DOI:10.1186/s13059-024-03197-8   PDF(Pubmed)

Abstract:
Early embryonic developmental programs are guided by the coordinated interplay between maternally inherited and zygotically manufactured RNAs and proteins. Although these processes happen concomitantly and affecting gene function during this period is bound to affect both pools of mRNAs, it has been challenging to study their expression dynamics separately.
By employing SLAM-seq, a nascent mRNA labeling transcriptomic approach, in a developmental time series we observe that over half of the early zebrafish embryo transcriptome consists of maternal-zygotic genes, emphasizing their pivotal role in early embryogenesis. We provide an hourly resolution of de novo transcriptional activation events and follow nascent mRNA trajectories, finding that most de novo transcriptional events are stable throughout this period. Additionally, by blocking microRNA-430 function, a key post transcriptional regulator during zebrafish embryogenesis, we directly show that it destabilizes hundreds of de novo transcribed mRNAs from pure zygotic as well as maternal-zygotic genes. This unveils a novel miR-430 function during embryogenesis, fine-tuning zygotic gene expression.
These insights into zebrafish early embryo transcriptome dynamics emphasize the significance of post-transcriptional regulators in zygotic genome activation. The findings pave the way for future investigations into the coordinated interplay between transcriptional and post-transcriptional landscapes required for the establishment of animal cell identities and functions.
摘要:
背景:早期胚胎发育程序受母系遗传和合子制造的RNA和蛋白质之间的协调相互作用指导。尽管这些过程同时发生,并且在此期间影响基因功能必然会影响两个mRNA库,分别研究它们的表达动力学一直具有挑战性。
结果:通过使用SLAM-seq,一种新生的mRNA标记转录组学方法,在发育时间序列中,我们观察到超过一半的早期斑马鱼胚胎转录组由母体合子基因组成,强调它们在早期胚胎发生中的关键作用。我们提供从头转录激活事件的每小时分辨率,并遵循新生的mRNA轨迹,发现大多数从头转录事件在此期间是稳定的。此外,通过阻断microRNA-430的功能,斑马鱼胚胎发育过程中的一个关键转录后调节因子,我们直接表明,它使来自纯合子和母系合子基因的数百种从头转录的mRNA不稳定。这揭示了一个新的miR-430在胚胎发生过程中的功能,微调合子基因表达。
结论:这些对斑马鱼早期胚胎转录组动态的认识强调了转录后调节因子在合子基因组激活中的重要性。这些发现为将来研究建立动物细胞身份和功能所需的转录和转录后景观之间的协调相互作用铺平了道路。
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