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

First Author  Miao X Year  2020
Journal  Mol Reprod Dev Volume  87
Issue  11 Pages  1152-1158
PubMed ID  33022126 Mgi Jnum  J:299155
Mgi Id  MGI:6490086 Doi  10.1002/mrd.23427
Citation  Miao X, et al. (2020) Loss of POLR1D results in embryonic lethality prior to blastocyst formation in mice. Mol Reprod Dev 87(11):1152-1158
abstractText  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.
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