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Nucleic Acids Research, 2003, Vol. 31, No. 21 6148-6156
© 2003 Oxford University Press

A role for c-Myc in the regulation of ribosomal RNA processing

Isabel Schlosser, Michael Hölzel, Marlies Mürnseer, Helmut Burtscher1, Ulrich H. Weidle1 and Dirk Eick*

GSF National Research Centre for Environment and Health, Institute of Clinical Molecular Biology and Tumor Genetics, Marchioninistraße 25, 81377 Munich, Germany and 1 Roche Diagnostics GmbH, Department TR-ON, 82372 Penzberg, Germany

*To whom correspondence should be addressed. Tel: +49 89 7099512; Fax: +49 89 7099500; Email: eick{at}gsf.de

The proto-oncogene c-myc encodes a basic helix–loop–helix leucine zipper transcription factor (c-Myc) that has a profound role in growth control and cell cycle progression. Previous microarray studies identified various classes of c-Myc target genes, including genes involved in ribosome biogenesis. By screening the human B-cell line P493-6 and rat fibroblasts conditionally expressing c-Myc, we could substantially extend the list of c-Myc target genes, particularly those required for ribosome biogenesis. The identification of 38 new c-Myc target genes with nucleolar function, prompted us to investigate processing of ribosomal RNA (rRNA). Using pulse–chase labelling experiments we show that c-Myc regulates the efficiency of rRNA maturation. In serum-stimulated P493-6 cells, only the processing of the 47S rRNA precursor to mature 18S and 28S rRNA, but not the synthesis of the 47S transcript, was dependent on the presence of c-Myc. As processing of rRNA is sensitive to inhibition of cyclin-dependent kinase (cdk) activity by roscovitine, we conclude that c-Myc regulates cell growth and proliferation by the coordinated induction of cdk activity and rRNA processing.


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