Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Genome Res. 2024 Sep 20;34(8):1235-1252. doi: 10.1101/gr.278980.124.
During embryonic development, cells undergo dynamic changes in gene expression that are required for appropriate cell fate specification. Although both transcription and mRNA degradation contribute to gene expression dynamics, patterns of mRNA decay are less well understood. Here, we directly measure spatiotemporally resolved mRNA decay rates transcriptome-wide throughout embryogenesis by transcription inhibition followed by bulk and single-cell RNA sequencing. This allows us to calculate mRNA half-lives within specific cell types and developmental stages, and identify differentially regulated mRNA decay throughout embryonic development. We identify transcript features that are correlated with mRNA stability and find that mRNA decay rates are associated with distinct peaks in gene expression over time. Moreover, we provide evidence that, on average, mRNA is more stable in the germline than in the soma and in later embryonic stages than in earlier stages. This work suggests that differential mRNA decay across cell states and time helps to shape developmental gene expression, and it provides a valuable resource for studies of mRNA turnover regulatory mechanisms.
在胚胎发育过程中,细胞经历基因表达的动态变化,这是适当的细胞命运特化所必需的。尽管转录和 mRNA 降解都有助于基因表达的动态变化,但 mRNA 衰减的模式还不太清楚。在这里,我们通过转录抑制,然后进行批量和单细胞 RNA 测序,直接测量整个胚胎发生过程中时空分辨率的 mRNA 衰减率的转录组范围。这使我们能够计算特定细胞类型和发育阶段内的 mRNA 半衰期,并识别整个胚胎发育过程中差异调节的 mRNA 衰减。我们确定了与 mRNA 稳定性相关的转录特征,并发现 mRNA 衰减率与随时间表达的基因的明显峰值相关。此外,我们提供的证据表明,mRNA 在生殖细胞中的稳定性平均高于体细胞,在胚胎后期的稳定性高于早期。这项工作表明,细胞状态和时间上的差异 mRNA 衰减有助于塑造发育中的基因表达,并为研究 mRNA 周转调节机制提供了有价值的资源。