Stowers Institute for Medical Research, 1000 E 50th Street, Kansas City, MO, 64110, USA.
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS, 66160, USA.
Genome Biol. 2024 Mar 19;25(1):74. doi: 10.1186/s13059-024-03197-8.
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.
早期胚胎发育程序是由母源性和合子性制造的 RNA 和蛋白质之间的协调相互作用指导的。虽然这些过程同时发生，并且在此期间影响基因功能必然会影响这两种 mRNA 池，但分别研究它们的表达动态一直具有挑战性。
通过在发育时间序列中使用 SLAM-seq，一种新生 mRNA 标记转录组学方法，我们观察到早期斑马鱼胚胎转录组的一半以上由母源-合子基因组成，强调了它们在早期胚胎发生中的关键作用。我们提供了从头转录激活事件的每小时分辨率，并跟踪新生 mRNA 轨迹，发现大多数从头转录事件在此期间都是稳定的。此外，通过阻断 microRNA-430 的功能，microRNA-430 是斑马鱼胚胎发生过程中的一个关键转录后调控因子，我们直接表明它会使纯合子和母源-合子基因的数百个新转录的 mRNA 不稳定。这揭示了 microRNA-430 在胚胎发生过程中的一个新功能，即精细调节合子基因表达。
这些对斑马鱼早期胚胎转录组动态的深入了解强调了转录后调控因子在合子基因组激活中的重要性。这些发现为未来研究动物细胞身份和功能建立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。
