Whole genome functional analysis identifies novel components required for mitotic spindle integrity in human cells

Daniel R. Rines, Maria Ana Gomez-Ferreria, Yingyao Zhou, Paul DeJesus, Seanna Grob, Serge Batalov, Marc Labow, Dieter Huesken, Craig Mickanin, Jonathan Hall, Mischa Reinhardt, Francois Natt, Joerg Lange, David J. Sharp, Sumit K. Chanda, Jeremy S. Caldwell

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52 Scopus citations

Abstract

Background: The mitotic spindle is a complex mechanical apparatus required for accurate segregation of sister chromosomes during mitosis. We designed a genetic screen using automated microscopy to discover factors essential for mitotic progression. Using a RNA interference library of 49,164 double-stranded RNAs targeting 23,835 human genes, we performed a loss of function screen to look for small interfering RNAs that arrest cells in metaphase. Results: Here we report the identification of genes that, when suppressed, result in structural defects in the mitotic spindle leading to bent, twisted, monopolar, or multipolar spindles, and cause cell cycle arrest. We further describe a novel analysis methodology for large-scale RNA interference datasets that relies on supervised clustering of these genes based on Gene Ontology, protein families, tissue expression, and protein-protein interactions. Conclusion: This approach was utilized to classify functionally the identified genes in discrete mitotic processes. We confirmed the identity for a subset of these genes and examined more closely their mechanical role in spindle architecture.

Original languageEnglish (US)
Article numberR44
JournalGenome biology
Volume9
Issue number2
DOIs
StatePublished - Feb 26 2008

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ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Cell Biology

Cite this

Rines, D. R., Gomez-Ferreria, M. A., Zhou, Y., DeJesus, P., Grob, S., Batalov, S., Labow, M., Huesken, D., Mickanin, C., Hall, J., Reinhardt, M., Natt, F., Lange, J., Sharp, D. J., Chanda, S. K., & Caldwell, J. S. (2008). Whole genome functional analysis identifies novel components required for mitotic spindle integrity in human cells. Genome biology, 9(2), [R44]. https://doi.org/10.1186/gb-2008-9-2-r44