A role for c-Myc in the regulation of ribosomal RNA processing.
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.
Schlosser
Isabel
I
GSF National Research Centre for Environment and Health, Institute of Clinical Molecular Biology and Tumor Genetics, Marchioninistrasse 25, 81377 Munich, Germany.
Hölzel
Michael
M
Mürnseer
Marlies
M
Burtscher
Helmut
H
Weidle
Ulrich H
UH
Eick
Dirk
D
D000818:Animals; D001402:B-Lymphocytes; D002453:Cell Cycle; D002460:Cell Line; D002466:Cell Nucleolus / Q000187:drug effects / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005347:Fibroblasts; D006801:Humans; D007700:Kinetics; D008934:Mitogens / Q000494:pharmacology; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D011687:Purines / Q000494:pharmacology; D012318:RNA Polymerase I / Q000378:metabolism; D012322:RNA Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D012335:RNA, Ribosomal / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012337:RNA, Ribosomal, 18S / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012339:RNA, Ribosomal, 28S / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012270:Ribosomes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000077546:Roscovitine; D013379:Substrate Specificity; D014158:Transcription, Genetic / Q000235:genetics
C000715470:MAS1 protein, human; D008934:Mitogens; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D011687:Purines; D012322:RNA Precursors; D012335:RNA, Ribosomal; D012337:RNA, Ribosomal, 18S; D012339:RNA, Ribosomal, 28S; D000077546:Roscovitine; D018844:Cyclin-Dependent Kinases; D012318:RNA Polymerase I