Abstract
BackgroundEssential for mitotic growth 1 (EMG1) is a highly conserved nucleolar protein identified in yeast to have a critical function in ribosome biogenesis. A mutation in the human EMG1 homolog causes Bowen-Conradi syndrome (BCS), a developmental disorder characterized by severe growth failure and psychomotor retardation leading to death in early childhood. To begin to understand the role of EMG1 in mammalian development, and how its deficiency could lead to Bowen-Conradi syndrome, we have used mouse as a model. The expression of Emg1 during mouse development was examined and mice carrying a null mutation for Emg1 were generated and characterized.ResultsOur studies indicated that Emg1 is broadly expressed during early mouse embryonic development. However, in late embryonic stages and during postnatal development, Emg1 exhibited specific expression patterns. To assess a developmental role for EMG1 in vivo, we exploited a mouse gene-targeting approach. Loss of EMG1 function in mice arrested embryonic development prior to the blastocyst stage. The arrested Emg1-/- embryos exhibited defects in early cell lineage-specification as well as in nucleologenesis. Further, loss of p53, which has been shown to rescue some phenotypes resulting from defects in ribosome biogenesis, failed to rescue the Emg1-/- pre-implantation lethality.ConclusionOur data demonstrate that Emg1 is highly expressed during mouse embryonic development, and essential for mouse pre-implantation development. The absolute requirement for EMG1 in early embryonic development is consistent with its essential role in yeast. Further, our findings also lend support to the previous study that showed Bowen-Conradi syndrome results from a partial EMG1 deficiency. A complete deficiency would not be expected to be compatible with a live birth.
Highlights
Essential for mitotic growth 1 (EMG1) is a highly conserved nucleolar protein identified in yeast to have a critical function in ribosome biogenesis
YEMG1 was found to interact directly with snoRNA [8] and the 18S ribosomal RNAs (rRNAs) [9]. These findings suggested that Yeast EMG1 (yEMG1) functions to methylate the 18S rRNA, a concept that was later supported by the identification of yEMG1 as a S-adenosyl methionine (SAM)-dependent pseudouridine-N1-specific methyltransferase [10]
Using RNA in situ hybridization, Emg1 expression was readily detected in E2.5 morula embryos (Figure 1A), with the strongest expression associated with the inside cells in the late stage of morula (Figure 1B)
Summary
Essential for mitotic growth 1 (EMG1) is a highly conserved nucleolar protein identified in yeast to have a critical function in ribosome biogenesis. The rRNA precursor (47S) is synthesized from the genes by RNA polymerase I and assembled with ribosomal proteins to form the 90S pre-ribosome. This 90S preribosome is matured to form the large-60S ribosomal subunit and the small-40S ribosomal subunit. Depletion of yEMG1 resulted in a reduction in 18S rRNA, a decrease in 40S ribosomal subunits and an increase in the ratio of 60S to 40S ribosomal subunits [5,6] These findings indicate an important role for EMG1 in the biogenesis of the 40S ribosome
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