Loss of POLR1D results in embryonic lethality prior to blastocyst formation in mice

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 thatPolr1dmutant embryos cannot be recovered at E7.5 early post-gastrulation stage, suggesting failed implantation. AlthoughPolr1dmutants 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 inPolr1dmutants. Additionally, lineage assessment reveals that trophectoderm specification is compromised in the absence ofPolr1d. In summary, these findings demonstrate the essential role of POLR1D during early mammalian embryogenesis and highlight cell-lethal phenotype withoutPolr1dfunction.