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Journal Article

Systematic genetic interaction screens uncover cell polarity regulators and functional redundancy.

MPS-Authors

Rodriguez,  Josana
Max Planck Society;

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Naganathan,  Sundar
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

Zeiser,  Eva
Max Planck Society;

Ishidate,  Takao
Max Planck Society;

Shirayama,  Masaki
Max Planck Society;

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Grill,  Stephan W.
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Citation

Fievet, B. T., Rodriguez, J., Naganathan, S., Lee, C., Zeiser, E., Ishidate, T., et al. (2013). Systematic genetic interaction screens uncover cell polarity regulators and functional redundancy. Nature Cell Biology, 15(1), 103-112.


Cite as: https://hdl.handle.net/21.11116/0000-0001-075A-3
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.