摘要：Abstract Bowen–Conradi syndrome (BCS) is a lethal autosomal recessive disorder caused by a {D86G} substitution in the protein, Essential for Mitotic Growth 1 (EMG1). {EMG1} is essential for 18S rRNA maturation and 40S ribosome biogenesis in yeast, but no studies of its role in ribosome biogenesis have been done in mammals. To assess the effect of the {EMG1} mutation on cell growth and ribosomal biogenesis in humans, we employed {BCS} patient cells. The {D86G} substitution did not interfere with {EMG1} nucleolar localization. In {BCS} patient lymphoblasts, cells accumulated in G2/M, resulting in reduced proliferation rates; however, patient fibroblasts showed normal proliferation. The rate of 18S rRNA processing was consistently delayed in patient cells, although this did not lead to a difference in the levels of 40S ribosomes, or a change in protein synthesis rates. These results demonstrate that as in yeast, {EMG1} in mammals has a role in ribosome biogenesis. The obvious phenotype in lymphoblasts compared to fibroblasts suggests a greater need for {EMG1} in rapidly dividing cells. Tissue-specific effects have been seen in other ribosomal biogenesis disorders, and it seems likely that the impact of {EMG1} deficiency would be larger in the rapidly proliferating cells of the developing embryo.
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