title: Heterozygous yeast deletion collection screens reveal essential targets of Hsp90.
abstract: Hsp90 is an essential eukaryotic chaperone with a role in folding specific "client" proteins such as kinases and hormone receptors. Previously performed homozygous diploid yeast deletion collection screens uncovered broad requirements for Hsp90 in cellular transport and cell cycle progression. These screens also revealed that the requisite cellular functions of Hsp90 change with growth temperature. We present here for the first time the results of heterozygous deletion collection screens conducted at the hypothermic stress temperature of 15°C. Extensive bioinformatic analyses were performed on the resulting data in combination with data from homozygous and heterozygous screens previously conducted at normal (30°C) and hyperthermic stress (37°C) growth temperatures. Our resulting meta-analysis uncovered extensive connections between Hsp90 and (1) general transcription, (2) ribosome biogenesis and (3) GTP binding proteins. Predictions from bioinformatic analyses were tested experimentally, supporting a role for Hsp90 in ribosome stability. Importantly, the integrated analysis of the 15°C heterozygous deletion pool screen with previously conducted 30°C and 37°C screens allows for essential genetic targets of Hsp90 to emerge. Altogether, these novel contributions enable a more complete picture of essential Hsp90 functions.
authors.affiliation: Bioinformatics Program, Boston University, Boston, Massachusetts, United States of America.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Franzosa
authors.forename: Véronique
authors.initials: V
authors.lastname: Albanèse
authors.forename: Judith
authors.initials: J
authors.lastname: Frydman
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.forename: Amie J
authors.initials: AJ
authors.lastname: McClellan
mesh_terms: D030541:Databases, Genetic; D019204:GTP-Binding Proteins / Q000378:metabolism; D017353:Gene Deletion; D053263:Gene Regulatory Networks / Q000235:genetics; D005820:Genetic Testing; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006579:Heterozygote; D006720:Homozygote; D016013:Likelihood Functions; D009687:Nuclear Proteins / Q000378:metabolism; D016366:Open Reading Frames / Q000235:genetics; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013696:Temperature
chemical_list: C436684:Bms1 protein, S cerevisiae; D018841:HSP90 Heat-Shock Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D019204:GTP-Binding Proteins