Genome-scale RNAi profiling of cell division in human tissue culture cells

Ralf Kittler, Laurence Pelletier, Anne Kristine Heninger, Mikolaj Slabicki, Mirko Theis, Lukasz Miroslaw, Ina Poser, Steffen Lawo, Hannes Grabner, Karol Kozak, Jan Wagner, Vineeth Surendranath, Constance Richter, Wayne Bowen, Aimee L. Jackson, Bianca Habermann, Anthony A. Hyman, Frank Buchholz

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235 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1401-1412
Number of pages12
JournalNature cell biology
Volume9
Issue number12
DOIs
StatePublished - Dec 1 2007

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ASJC Scopus subject areas

  • Cell Biology

Cite this

Kittler, R., Pelletier, L., Heninger, A. K., Slabicki, M., Theis, M., Miroslaw, L., Poser, I., Lawo, S., Grabner, H., Kozak, K., Wagner, J., Surendranath, V., Richter, C., Bowen, W., Jackson, A. L., Habermann, B., Hyman, A. A., & Buchholz, F. (2007). Genome-scale RNAi profiling of cell division in human tissue culture cells. Nature cell biology, 9(12), 1401-1412. https://doi.org/10.1038/ncb1659