title: Sch9 regulates ribosome biogenesis via Stb3, Dot6 and Tod6 and the histone deacetylase complex RPD3L.
abstract: TORC1 is a conserved multisubunit kinase complex that regulates many aspects of eukaryotic growth including the biosynthesis of ribosomes. The TOR protein kinase resident in TORC1 is responsive to environmental cues and is potently inhibited by the natural product rapamycin. Recent characterization of the rapamycin-sensitive phosphoproteome in yeast has yielded insights into how TORC1 regulates growth. Here, we show that Sch9, an AGC family kinase and direct substrate of TORC1, promotes ribosome biogenesis (Ribi) and ribosomal protein (RP) gene expression via direct inhibitory phosphorylation of the transcriptional repressors Stb3, Dot6 and Tod6. Deletion of STB3, DOT6 and TOD6 partially bypasses the growth and cell size defects of an sch9 strain and reveals interdependent regulation of both Ribi and RP gene expression, and other aspects of Ribi. Dephosphorylation of Stb3, Dot6 and Tod6 enables recruitment of the RPD3L histone deacetylase complex to repress Ribi/RP gene promoters. Taken together with previous studies, these results suggest that Sch9 is a master regulator of ribosome biogenesis through the control of Ribi, RP, ribosomal RNA and tRNA gene transcription.
authors: Department of Molecular Biology and National Center for Competence in Research Program 'Frontiers in Genetics', University of Geneva, Geneva, Switzerland.
authors: Alexandre
authors: A
authors: Huber
authors: Sarah L
authors: SL
authors: French
authors: Hille
authors: H
authors: Tekotte
authors: Seda
authors: S
authors: Yerlikaya
authors: Michael
authors: M
authors: Stahl
authors: Mariya P
authors: MP
authors: Perepelkina
authors: Mike
authors: M
authors: Tyers
authors: Jacques
authors: J
authors: Rougemont
authors: Ann L
authors: AL
authors: Beyer
authors: Robbie
authors: R
authors: Loewith
mesh_terms: D015966:Gene Expression Regulation, Fungal; D012335:RNA, Ribosomal / Q000096:biosynthesis*; D012343:RNA, Transfer / Q000096:biosynthesis; D012269:Ribosomal Proteins / Q000096:biosynthesis*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D012335:RNA, Ribosomal; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D012343:RNA, Transfer