title: Genome-scale RNAi profiling of cell division in human tissue culture cells.
abstract: Cell division is fundamental for all organisms. Here we report a genome-scale RNA-mediated interference screen in HeLa cells designed to identify human genes that are important for cell division. We have used a library of endoribonuclease-prepared short interfering RNAs for gene silencing and have used DNA content analysis to identify genes that induced cell cycle arrest or altered ploidy on silencing. Validation and secondary assays were performed to generate a nine-parameter loss-of-function phenoprint for each of the genes. These phenotypic signatures allowed the assignment of genes to specific functional classes by combining hierarchical clustering, cross-species analysis and proteomic data mining. We highlight the richness of our dataset by ascribing novel functions to genes in mitosis and cytokinesis. In particular, we identify two evolutionarily conserved transcriptional regulatory networks that govern cytokinesis. Our work provides an experimental framework from which the systematic analysis of novel genes necessary for cell division in human cells can begin.
authors.affiliation: Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D-01307 Dresden, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Kittler
authors.forename: Laurence
authors.initials: L
authors.lastname: Pelletier
authors.forename: Anne-Kristine
authors.initials: AK
authors.lastname: Heninger
authors.forename: Mikolaj
authors.initials: M
authors.lastname: Slabicki
authors.forename: Mirko
authors.initials: M
authors.lastname: Theis
authors.forename: Lukasz
authors.initials: L
authors.lastname: Miroslaw
authors.forename: Ina
authors.initials: I
authors.lastname: Poser
authors.forename: Steffen
authors.initials: S
authors.lastname: Lawo
authors.forename: Hannes
authors.initials: H
authors.lastname: Grabner
authors.forename: Karol
authors.initials: K
authors.lastname: Kozak
authors.forename: Jan
authors.initials: J
authors.lastname: Wagner
authors.forename: Vineeth
authors.initials: V
authors.lastname: Surendranath
authors.forename: Constance
authors.initials: C
authors.lastname: Richter
authors.forename: Wayne
authors.initials: W
authors.lastname: Bowen
authors.forename: Aimee L
authors.initials: AL
authors.lastname: Jackson
authors.forename: Bianca
authors.initials: B
authors.lastname: Habermann
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Hyman
authors.forename: Frank
authors.initials: F
authors.lastname: Buchholz
mesh_terms: D002455:Cell Division / Q000502:physiology*; D020869:Gene Expression Profiling; D015894:Genome, Human; D006367:HeLa Cells; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering