Genome-scale RNAi profiling of cell division in human tissue culture cells.
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.
Kittler
Ralf
R
Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D-01307 Dresden, Germany.
Pelletier
Laurence
L
Heninger
Anne-Kristine
AK
Slabicki
Mikolaj
M
Theis
Mirko
M
Miroslaw
Lukasz
L
Poser
Ina
I
Lawo
Steffen
S
Grabner
Hannes
H
Kozak
Karol
K
Wagner
Jan
J
Surendranath
Vineeth
V
Richter
Constance
C
Bowen
Wayne
W
Jackson
Aimee L
AL
Habermann
Bianca
B
Hyman
Anthony A
AA
Buchholz
Frank
F
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
D034741:RNA, Small Interfering