In eukaryotic cells, RNA polymerase (Pol) I and Pol III are dedicated to the synthesis of ribosomal RNA precursors and a variety of small RNAs, respectively. Although RNA Pol I and Pol III complexes are crucial for the regulation of cell growth and cell cycle in all cell types, many of the components of the Pol I and Pol III complexes have not been functionally characterized in mammals. Here, we provide the first in vivo functional characterization of POLR1D, a subunit shared by RNA Pol I and Pol III, during early mammalian embryo development. Our results show that Polr1d mutant embryos cannot be recovered at E7.5 early post‐gastrulation stage, suggesting failed implantation. Although Polr1d mutants can be recovered at E3.5, they exhibit delayed/stalled development with morula morphology rather than differentiation into blastocysts. Even with extended time in culture, mutant embryos fail to form blastocysts and eventually die. Analysis of E3.0 embryos revealed severe DNA damage in Polr1d mutants. Additionally, lineage assessment reveals that trophectoderm specification is compromised in the absence of Polr1d. In summary, these findings demonstrate the essential role of POLR1D during early mammalian embryogenesis and highlight cell‐lethal phenotype without Polr1d function.

中文翻译：

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POLR1D 缺失导致小鼠胚泡形成前胚胎致死

在真核细胞中，RNA 聚合酶 (Pol) I 和 Pol III 分别用于合成核糖体 RNA 前体和各种小 RNA。尽管 RNA Pol I 和 Pol III 复合物对于调节所有细胞类型的细胞生长和细胞周期至关重要，但 Pol I 和 Pol III 复合物的许多成分尚未在哺乳动物中进行功能表征。在这里，我们提供了 POLR1D 的第一个体内功能表征，POLR1D 是早期哺乳动物胚胎发育过程中由 RNA Pol I 和 Pol III 共享的亚基。我们的结果表明Polr1d突变体胚胎无法在 E7.5 早期原肠胚形成阶段恢复，表明植入失败。虽然Polr1d突变体可以在 E3.5 恢复，它们表现出延迟/停滞的发育与桑椹胚形态而不是分化为囊胚。即使在培养中延长时间，突变胚胎也无法形成囊胚并最终死亡。E3.0 胚胎的分析揭示了Polr1d突变体中的严重 DNA 损伤。此外，谱系评估表明，在没有Polr1d的情况下，滋养外胚层的规格会受到影响。总之，这些发现证明了 POLR1D 在早期哺乳动物胚胎发生过程中的重要作用，并突出了没有Polr1d功能的细胞致死表型。