title: Integrated RNA- and protein profiling of fermentation and respiration in diploid budding yeast provides insight into nutrient control of cell growth and development.
abstract: Diploid budding yeast undergoes rapid mitosis when it ferments glucose, and in the presence of a non-fermentable carbon source and the absence of a nitrogen source it triggers sporulation. Rich medium with acetate is a commonly used pre-sporulation medium, but our understanding of the molecular events underlying the acetate-driven transition from mitosis to meiosis is still incomplete. We identified 263 proteins for which mRNA and protein synthesis are linked or uncoupled in fermenting and respiring cells. Using motif predictions, interaction data and RNA profiling we find among them 28 likely targets for Ume6, a subunit of the conserved Rpd3/Sin3 histone deacetylase-complex regulating genes involved in metabolism, stress response and meiosis. Finally, we identify 14 genes for which both RNA and proteins are detected exclusively in respiring cells but not in fermenting cells in our sample set, including CSM4, SPR1, SPS4 and RIM4, which were thought to be meiosis-specific. Our work reveals intertwined transcriptional and post-transcriptional control mechanisms acting when a MATa/α strain responds to nutritional signals, and provides molecular clues how the carbon source primes yeast cells for entering meiosis.
  
  
  CONCLUSIONS
  Our integrated genomics study provides insight into the interplay between the transcriptome and the proteome in diploid yeast cells undergoing vegetative growth in the presence of glucose (fermentation) or acetate (respiration). Furthermore, it reveals novel target genes involved in these processes for Ume6, the DNA binding subunit of the conserved histone deacetylase Rpd3 and the co-repressor Sin3. We have combined data from an RNA profiling experiment using tiling arrays that cover the entire yeast genome, and a large-scale protein detection analysis based on mass spectrometry in diploid MATa/α cells. This distinguishes our study from most others in the field-which investigate haploid yeast strains-because only diploid cells can undergo meiotic development in the simultaneous absence of a non-fermentable carbon source and nitrogen. Indeed, we report molecular clues how respiration of acetate might prime diploid cells for efficient spore formation, a phenomenon that is well known but poorly understood.
authors: Inserm U1085 IRSET, Université de Rennes 1, 35042 Rennes, France.
authors: Emmanuelle
authors: E
authors: Becker
authors: Inserm U1085 IRSET, Université de Rennes 1, 35042 Rennes, France.
authors: Yuchen
authors: Y
authors: Liu
authors: Inserm U1085 IRSET, Université de Rennes 1, 35042 Rennes, France.
authors: Aurélie
authors: A
authors: Lardenois
authors: Inserm U1085 IRSET, Université de Rennes 1, 35042 Rennes, France.
authors: Thomas
authors: T
authors: Walther
authors: Stanford Genome Technology Center, Palo Alto, CA 94304, USA.
authors: Joe
authors: J
authors: Horecka
authors: Inserm U1085 IRSET, Université de Rennes 1, 35042 Rennes, France.
authors: Igor
authors: I
authors: Stuparevic
authors: Rowan University, School of Osteopathic Medicine, Stratford, NJ 08084, USA.
authors: Michael J
authors: MJ
authors: Law
authors: Inserm U1085 IRSET, Proteomics Core Facility Biogenouest, Université de Rennes 1, 35042 Rennes, France.
authors: Régis
authors: R
authors: Lavigne
authors: Inserm U1085 IRSET, Université de Rennes 1, 35042 Rennes, France.
authors: Bertrand
authors: B
authors: Evrard
authors: Biozentrum, University of Basel, Basel CH-4056, Switzerland.
authors: Philippe
authors: P
authors: Demougin
authors: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
authors: Michael
authors: M
authors: Riffle
authors: Rowan University, School of Osteopathic Medicine, Stratford, NJ 08084, USA.
authors: Randy
authors: R
authors: Strich
authors: Stanford Genome Technology Center, Palo Alto, CA 94304, USA; Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.
authors: Ronald W
authors: RW
authors: Davis
authors: Inserm U1085 IRSET, Université de Rennes 1, 35042 Rennes, France; Inserm U1085 IRSET, Proteomics Core Facility Biogenouest, Université de Rennes 1, 35042 Rennes, France.
authors: Charles
authors: C
authors: Pineau
authors: Inserm U1085 IRSET, Université de Rennes 1, 35042 Rennes, France. Electronic address: michael.primig@inserm.fr.
authors: Michael
authors: M
authors: Primig
mesh_terms: D004171:Diploidy; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D012331:RNA, Fungal / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis*
chemical_list: D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins
keywords: Fermentation; Proteome; Respiration; Rim4; Transcriptome; Ume6