Robert Steinbauer

Regulation of Ribosome Biogenesis and Rna Polymerase I Transcription: How Nutrients Control the Synthesis of Ribosomes Robert Steinbauer

Ribosome synthesis depends on nutrient availability sensed by the target of rapamycin (TOR) signaling pathway in eukaryotic cells. TOR inactivation affects ribosome biogenesis at the level of RNA polymerase I (Pol I)-dependent transcription of ribosomal RNA (rRNA) genes, expression of ribosomal proteins (r-proteins) and ribosome biogenesis factors, pre-ribosome processing, and transport. Detailed analysis shows that upon TOR inactivation the levels of newly synthesized ribosomal subunits drop drastically before the integrity of the Pol I apparatus is severely impaired but in good correlation with a sharp decrease in r-protein production. Inhibition of translation by cycloheximide mimics the rRNA maturation defect observed immediately after TOR inactivation. Both cycloheximide addition and the depletion of individual r-proteins also reproduce TOR-dependent nucleolar entrapment of specific ribosomal precursor complexes. The conclusion could be drawn that shortage of newly synthesized r-proteins after short-term TOR inactivation is sufficient to explain most of the observed effects on ribosome production.