Regulation of ribosome biogenesis by the rapamycin-sensitive TOR-signaling pathway in Saccharomyces cerevisiae.
The TOR (target of rapamycin) signal transduction pathway is an important mechanism by which cell growth is controlled in all eucaryotic cells. Specifically, TOR signaling adjusts the protein biosynthetic capacity of cells according to nutrient availability. In mammalian cells, one branch of this pathway controls general translational initiation, whereas a separate branch specifically regulates the translation of ribosomal protein (r-protein) mRNAs. In Saccharomyces cerevisiae, the TOR pathway similarly regulates general translational initiation, but its specific role in the synthesis of ribosomal components is not well understood. Here we demonstrate that in yeast control of ribosome biosynthesis by the TOR pathway is surprisingly complex. In addition to general effects on translational initiation, TOR exerts drastic control over r-protein gene transcription as well as the synthesis and subsequent processing of 35S precursor rRNA. We also find that TOR signaling is a prerequisite for the induction of r-protein gene transcription that occurs in response to improved nutrient conditions. This induction has been shown previously to involve both the Ras-adenylate cyclase as well as the fermentable growth medium-induced pathways, and our results therefore suggest that these three pathways may be intimately linked.
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Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California, School of Medicine, San Francisco, California 94143-0448, USA. tpowers@socrates.ucsf.edu
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D000262:Adenylyl Cyclases / Q000378:metabolism; D018797:Cell Cycle Proteins; D005656:Fungal Proteins / Q000378:metabolism*; D010442:Peptide Chain Initiation, Translational; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011132:Polyribosomes / Q000502:physiology; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics*; D012335:RNA, Ribosomal / Q000096:biosynthesis / Q000235:genetics*; D012269:Ribosomal Proteins / Q000235:genetics*; D012270:Ribosomes / Q000502:physiology* / Q000648:ultrastructure*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology*; D014158:Transcription, Genetic; D018631:ras Proteins / Q000378:metabolism
D000262:Adenylyl Cyclases; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D012333:RNA, Messenger; D012335:RNA, Ribosomal; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus; D018631:ras Proteins; C083324:TOR1 protein, S cerevisiae; C081135:TOR2 protein, S cerevisiae