Ribosomal protein L11 associates with c-Myc at 5 S rRNA and tRNA genes and regulates their expression

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Abstract

The c-Myc oncoprotein promotes cell growth by enhancing ribosomal biogenesis. Overexpression of c-Myc and aberrant ribosomal biogenesis lead to deregulated cell growth and tumorigenesis. Hence, c-Myc activity and ribosomal biogenesis must be tightly coordinated during normal homeostasis. We previously found that ribosomal protein L11 inhibits c-Myc activity by blocking the recruitment of its co-activator transformation/transcription domain-associated protein (TRRAP) to the promoter regions of c-Myc target genes that are transcribed by RNA polymerases I and II. In this study, we extended the role of L11 to the regulation of c-Myc-driven transcription of the 5 S rRNA and tRNA genes by RNA polymerase III. L11 co-resided with c-Myc at the 5 S rRNA and tRNA genes and significantly inhibited the binding of TRRAP to these genes. Knocking down endogenous L11 enhanced c-Myc-dependent transcription of these genes. Interestingly, in response to ribosomal stress induced by the treatment of cells with a low dose of actinomycin D or serum starvation, L11 binding to these genes was increased, and inversely TRRAP binding to these genes was decreased. Consistently, knockdown of L11 rescued the reduction of the expression of these genes by the two treatments. These results demonstrate that L11 suppresses c-Myc-dependent and RNA polymerase III-catalyzed transcription of 5 S rRNA and tRNA genes in response to ribosomal stress, ensuring a tight coordination between c-Myc activity and ribosomal biogenesis.

Original languageEnglish (US)
Pages (from-to)12587-12594
Number of pages8
JournalJournal of Biological Chemistry
Volume285
Issue number17
DOIs
StatePublished - Apr 23 2010

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Transfer RNA
rRNA Genes
RNA Polymerase III
Genes
Transcription
Personnel Selection
RNA Polymerase I
myc Genes
RNA Polymerase II
Oncogene Proteins
Dactinomycin
Growth
Starvation
Genetic Promoter Regions
Protein Binding
Carcinogenesis
Homeostasis
Cell growth
Gene Expression
Serum

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Ribosomal protein L11 associates with c-Myc at 5 S rRNA and tRNA genes and regulates their expression. / Dai, Mushui; Sun, Xiao-Xin; Lu, Hua.

In: Journal of Biological Chemistry, Vol. 285, No. 17, 23.04.2010, p. 12587-12594.

Research output: Contribution to journalArticle

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