RESEARCH ARTICLE A Genome-Wide siRNA Screen in Mammalian Cells for Regulators of S6 Phosphorylation Angela Papageorgiou1,2,3, Joseph Rapley1,2,3, Jill P. Mesirov4, Pablo Tamayo4, Joseph Avruch1,2,3* 1 Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, 02114, United States of America, 2 Diabetes Unit, Medical Services, Massachusetts General Hospital, Boston, MA, 02114, United States of America, 617–726–6909, 3 Department of Medicine, Harvard Medical School, Boston, MA, 02115, United States of America, 4 Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts, 02142, United States of America *
[email protected] Abstract mTOR complex1, the major regulator of mRNA translation in all eukaryotic cells, is strongly activated in most cancers. We performed a genome-wide RNAi screen in a human cancer cell line, seeking genes that regulate S6 phosphorylation, readout of mTORC1 activity. Ap- plying a stringent selection, we retrieved nearly 600 genes wherein at least two RNAis gave OPEN ACCESS significant reduction in S6-P. This cohort contains known regulators of mTOR complex 1 Citation: Papageorgiou A, Rapley J, Mesirov JP, and is significantly enriched in genes whose depletion affects the proliferation/viability of the Tamayo P, Avruch J (2015) A Genome-Wide siRNA large set of cancer cell lines in the Achilles database in a manner paralleling that caused by Screen in Mammalian Cells for Regulators of S6 Phosphorylation. PLoS ONE 10(3): e0116096. mTOR depletion. We next examined the effect of RNAi pools directed at 534 of these gene doi:10.1371/journal.pone.0116096 products on S6-P in TSC1 null mouse embryo fibroblasts.