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.
GSF National Research Centre for Environment and Health, Institute of Clinical Molecular Biology and Tumor Genetics, Marchioninistrasse 25, 81377 Munich, Germany.
Isabel
I
Schlosser
Michael
M
Hölzel
Marlies
M
Mürnseer
Helmut
H
Burtscher
Ulrich H
UH
Weidle
Dirk
D
Eick
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