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Etude des propriétés enzymatiques et du rôle dans la biogénèse des ribosomes de la protéine humaine p120, marqueur de l'évolution tumorale, et de Nop2p son homologue chez Saccharomyces cerevisiae

Abstract : The protein p120 is a proliferation marker that was originally identified in human tumor cells. The yeast homologue of p120, nucleolar protein Nop2p, was shown to be essential for viability of yeast. Alignment of Nop2p with human p120 points out the evolutionary conservation of a large domain that contains a SAM-binding motif and a protein domain having potential RNA: m5C-méthyltransférase activity. By in vitro methylation experiments and a sodium bisulfite approach, we show that Nop2p is a RNA: m5C-methyltransferase specific for 25S rRNA nucleotide 2870. In parallel, we succeeded to complement Nop2-deficient yeasts by human p120 and studied the importance of different sequence and structural domains of Nop2 and p120 for rRNA processing in vivo. In complementation assays, the C-terminal domain of Nop2 was essential for cell viability, whereas the absence of the N-terminal domain led to slow growth phenotype. Chimeric proteins formed by Nop2 and p120 fragments efficiently support growth if the N-terminal domain of Nop2 was present. In the absence of Nop2 or p120, the C1/C2 cleavages required to generate 5.8S and 25S rRNA were strongly reduced. The reduction of p120 content in human cells by specific siRNA leads to decreased 28S rRNA accumulation, supporting the idea on the implication of p120 in human pre-rRNA processing
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https://hal.univ-lorraine.fr/tel-01746261
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Gabrielle Bourgeois. Etude des propriétés enzymatiques et du rôle dans la biogénèse des ribosomes de la protéine humaine p120, marqueur de l'évolution tumorale, et de Nop2p son homologue chez Saccharomyces cerevisiae. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2011. Français. ⟨NNT : 2011NAN10110⟩. ⟨tel-01746261⟩

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