Ribosomal protein S6 kinase activity controls the ribosome biogenesis transcriptional program
C Chauvin1, V Koka1, A Nouschi1
11] INSERM, U845, Paris, France [2] Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, UMRS-845, Paris, France.
Oncogene
|January 16, 2013
Summary
S6 kinases (S6Ks) control the ribosome biogenesis transcriptional program. This process is rpS6 kinase-dependent and distinct from ribosomal protein synthesis regulation.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- S6 kinases (S6Ks) are key regulators of cell growth downstream of mTOR.
- S6Ks phosphorylate ribosomal protein S6 (rpS6) and other translational machinery components.
- The precise roles of S6K-mediated phosphorylation in gene expression remain incompletely understood.
Purpose of the Study:
- To investigate the role of S6Ks in transcriptional and translational regulation of gene expression.
- To elucidate the S6K-dependent control of ribosome biogenesis (RiBi).
Main Methods:
- Whole-genome microarray analysis of total and polysomal mouse liver RNA after feeding.
- Comparison of gene expression profiles in wild-type and S6K1;S6K2(-/-) knockout mice.
- Analysis of rpS6 knock-in mutants unable to be phosphorylated.
Main Results:
- Mice lacking S6K1 and S6K2 exhibit a defect in the feeding-induced RiBi transcriptional program.
- Over 75% of RiBi factors, including specific nucleolar proteins, are S6K-controlled.
- Impaired RiBi transcriptional promoter activity in S6K-deficient cells mirrors that in rpS6 mutants lacking phosphorylation sites.
- Ribosomal protein synthesis rates are unaffected by these mutations.
Conclusions:
- S6K activity specifically regulates the transcriptional program of ribosome biogenesis (RiBi).
- This RiBi transcriptional control is mediated through rpS6 kinase activity, independent of ribosomal protein synthesis levels.
- Reveals a distinct function of rpS6 kinase activity in orchestrating the RiBi transcriptional program.
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