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

Nucleic Acids Res. 2003 Nov 1;31(21):6148-56. doi: 10.1093/nar/gkg794.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes
  • Cell Cycle
  • Cell Line
  • Cell Nucleolus / drug effects
  • Cell Nucleolus / genetics
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Cyclin-Dependent Kinases / metabolism
  • Fibroblasts
  • Humans
  • Kinetics
  • Mitogens / pharmacology
  • Models, Genetic
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Purines / pharmacology
  • RNA Polymerase I / metabolism
  • RNA Precursors / chemistry
  • RNA Precursors / genetics
  • RNA Precursors / metabolism*
  • RNA Processing, Post-Transcriptional* / drug effects
  • RNA, Ribosomal / biosynthesis
  • RNA, Ribosomal / chemistry
  • RNA, Ribosomal / genetics
  • RNA, Ribosomal / metabolism*
  • RNA, Ribosomal, 18S / biosynthesis
  • RNA, Ribosomal, 18S / chemistry
  • RNA, Ribosomal, 18S / genetics
  • RNA, Ribosomal, 18S / metabolism
  • RNA, Ribosomal, 28S / biosynthesis
  • RNA, Ribosomal, 28S / chemistry
  • RNA, Ribosomal, 28S / genetics
  • RNA, Ribosomal, 28S / metabolism
  • Rats
  • Ribosomes / drug effects
  • Ribosomes / genetics
  • Ribosomes / metabolism
  • Roscovitine
  • Substrate Specificity
  • Transcription, Genetic / genetics

Substances

  • MAS1 protein, human
  • Mitogens
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-myc
  • Purines
  • RNA Precursors
  • RNA, Ribosomal
  • RNA, Ribosomal, 18S
  • RNA, Ribosomal, 28S
  • Roscovitine
  • Cyclin-Dependent Kinases
  • RNA Polymerase I