Systematic genetic interaction screens uncover cell polarity regulators and functional redundancy

Although single gene loss of function analyses can identify components of particular processes, important molecules are missed due 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 C. 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 homologs. We experimentally confirmed functional roles predicted by the network and characterised 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.