title: shRNA-mediated RNA interference as a tool for genetic synthetic lethality screening in mouse embryo fibroblasts.
abstract: Previously, we demonstrated the establishment of synthetic lethality screening in cultured somatic human cells, or mouse embryo fibroblasts (MEFs), for chemicals or mutant genes synergistically lethal with a mutated gene of interest. Here, we show in MEFs that the usage of RNA interference-based genetic suppressor elements encoding short hairpin RNAs (shRNAs) enables for genetic synthetic lethality screening at a frequency much higher than that achieved before with short truncated sense and antisense RNAs. These findings open up the possibility of using in mammalian cells genome-wide shRNA libraries for genetic synthetic lethality screening at the multi-gene level.
authors.affiliation: Department of Biochemistry, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Israel.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Einav
authors.forename: Reuven
authors.initials: R
authors.lastname: Agami
authors.forename: Dan
authors.initials: D
authors.lastname: Canaani
mesh_terms: D000818:Animals; D019731:Carbon-Nitrogen Ligases / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism; D005804:Genes, Lethal / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics; D023281:Genomics / Q000379:methods*; D051379:Mice; D010957:Plasmids / Q000235:genetics; D011687:Purines / Q000096:biosynthesis; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics*
chemical_list: D011687:Purines; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019731:Carbon-Nitrogen Ligases; C020828:GMP synthase (glutamine-hydrolyzing); C030985:purine