title: Exploration of essential gene functions via titratable promoter alleles.
abstract: Nearly 20% of yeast genes are required for viability, hindering genetic analysis with knockouts. We created promoter-shutoff strains for over two-thirds of all essential yeast genes and subjected them to morphological analysis, size profiling, drug sensitivity screening, and microarray expression profiling. We then used this compendium of data to ask which phenotypic features characterized different functional classes and used these to infer potential functions for uncharacterized genes. We identified genes involved in ribosome biogenesis (HAS1, URB1, and URB2), protein secretion (SEC39), mitochondrial import (MIM1), and tRNA charging (GSN1). In addition, apparent negative feedback transcriptional regulation of both ribosome biogenesis and the proteasome was observed. We furthermore show that these strains are compatible with automated genetic analysis. This study underscores the importance of analyzing mutant phenotypes and provides a resource to complement the yeast knockout collection.
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, 112 College Street, Toronto, ON M5G 1L6, Canada.
authors.forename: Sanie
authors.initials: S
authors.lastname: Mnaimneh
authors.forename: Armaity P
authors.initials: AP
authors.lastname: Davierwala
authors.forename: Jennifer
authors.initials: J
authors.lastname: Haynes
authors.forename: Jason
authors.initials: J
authors.lastname: Moffat
authors.forename: Wen-Tao
authors.initials: WT
authors.lastname: Peng
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Xueqi
authors.initials: X
authors.lastname: Yang
authors.forename: Jeff
authors.initials: J
authors.lastname: Pootoolal
authors.forename: Gordon
authors.initials: G
authors.lastname: Chua
authors.forename: Andres
authors.initials: A
authors.lastname: Lopez
authors.forename: Miles
authors.initials: M
authors.lastname: Trochesset
authors.forename: Darcy
authors.initials: D
authors.lastname: Morse
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
authors.forename: Shawna L
authors.initials: SL
authors.lastname: Hiley
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Li
authors.forename: Quaid
authors.initials: Q
authors.lastname: Morris
authors.forename: Jörg
authors.initials: J
authors.lastname: Grigull
authors.forename: Nicholas
authors.initials: N
authors.lastname: Mitsakakis
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Roberts
authors.forename: Jack F
authors.initials: JF
authors.lastname: Greenblatt
authors.forename: Charles
authors.initials: C
authors.lastname: Boone
authors.forename: Chris A
authors.initials: CA
authors.lastname: Kaiser
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Andrews
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Hughes
mesh_terms: D000483:Alleles; D025461:Feedback, Physiological; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D020043:Genes, Essential; D005800:Genes, Fungal; D008928:Mitochondria / Q000378:metabolism; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D004364:Pharmaceutical Preparations / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D012343:RNA, Transfer / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004364:Pharmaceutical Preparations; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D012343:RNA, Transfer