title: Reduction in ribosomal protein synthesis is sufficient to explain major effects on ribosome production after short-term TOR inactivation in Saccharomyces cerevisiae.
abstract: Ribosome synthesis depends on nutrient availability, sensed by the target of rapamycin (TOR) signaling pathway in eukaryotes. TOR inactivation affects ribosome biogenesis at the level of rRNA gene transcription, expression of ribosomal proteins (r-proteins) and biogenesis factors, preribosome processing, and transport. Here, we demonstrate that upon TOR inactivation, levels of newly synthesized ribosomal subunits drop drastically before the integrity of the RNA polymerase 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. We suggest that shortage of newly synthesized r-proteins after short-term TOR inactivation is sufficient to explain most of the observed effects on ribosome production.
authors.affiliation: Universitaet Regensburg, Institut für Biochemie, Genetik und Mikrobiologie, Lehrstuhl Biochemie III, Regensburg, Germany.
authors.forename: Alarich
authors.initials: A
authors.lastname: Reiter
authors.forename: Robert
authors.initials: R
authors.lastname: Steinbauer
authors.forename: Anja
authors.initials: A
authors.lastname: Philippi
authors.forename: Jochen
authors.initials: J
authors.lastname: Gerber
authors.forename: Herbert
authors.initials: H
authors.lastname: Tschochner
authors.forename: Philipp
authors.initials: P
authors.lastname: Milkereit
authors.forename: Joachim
authors.initials: J
authors.lastname: Griesenbeck
mesh_terms: D001483:Base Sequence; D003513:Cycloheximide / Q000494:pharmacology; D004271:DNA, Fungal / Q000235:genetics; D005800:Genes, Fungal; D020459:Genes, rRNA; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012318:RNA Polymerase I / Q000378:metabolism; D012322:RNA Precursors / Q000096:biosynthesis / Q000235:genetics; D012331:RNA, Fungal / Q000096:biosynthesis / Q000235:genetics; D012269:Ribosomal Proteins / Q000096:biosynthesis*; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology
chemical_list: D004271:DNA, Fungal; D012322:RNA Precursors; D012331:RNA, Fungal; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D003513:Cycloheximide; D017346:Protein Serine-Threonine Kinases; C500749:target of rapamycin protein, S cerevisiae; D012318:RNA Polymerase I; D020123:Sirolimus