title: Systematic genetic interaction screens uncover cell polarity regulators and functional redundancy.
abstract: Although single-gene loss-of-function analyses can identify components of particular processes, important molecules are missed owing to the robustness of biological systems. Here we show that large-scale RNAi screening for suppression interactions with functionally related mutants greatly expands the repertoire of genes known to act in a shared process and reveals a new layer of functional relationships. We performed RNAi screens for 17 Caenorhabditis elegans cell polarity mutants, generating the most comprehensive polarity network in a metazoan, connecting 184 genes. Of these, 72% were not previously linked to cell polarity and 80% have human homologues. We experimentally confirmed functional roles predicted by the network and characterized through biophysical analyses eight myosin regulators. In addition, we discovered functional redundancy between two unknown polarity genes. Similar systematic genetic interaction screens for other biological processes will help uncover the inventory of relevant genes and their patterns of interactions.
authors.affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge CB2 1QN, UK.
authors.forename: Bruno Thomas
authors.initials: BT
authors.lastname: Fievet
authors.forename: Josana
authors.initials: J
authors.lastname: Rodriguez
authors.forename: Sundar
authors.initials: S
authors.lastname: Naganathan
authors.forename: Christine
authors.initials: C
authors.lastname: Lee
authors.forename: Eva
authors.initials: E
authors.lastname: Zeiser
authors.forename: Takao
authors.initials: T
authors.lastname: Ishidate
authors.forename: Masaki
authors.initials: M
authors.lastname: Shirayama
authors.forename: Stephan
authors.initials: S
authors.lastname: Grill
authors.forename: Julie
authors.initials: J
authors.lastname: Ahringer
mesh_terms: D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D016764:Cell Polarity / Q000235:genetics*; D004625:Embryo, Nonmammalian / Q000166:cytology; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D017238:Genes, Helminth; D005804:Genes, Lethal; D058977:Molecular Sequence Annotation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; C087977:par-2 protein, C elegans; D000205:Actomyosin; D011494:Protein Kinases