title: Comparative RNAi screening identifies a conserved core metazoan actinome by phenotype.
abstract: Although a large number of actin-binding proteins and their regulators have been identified through classical approaches, gaps in our knowledge remain. Here, we used genome-wide RNA interference as a systematic method to define metazoan actin regulators based on visual phenotype. Using comparative screens in cultured Drosophila and human cells, we generated phenotypic profiles for annotated actin regulators together with proteins bearing predicted actin-binding domains. These phenotypic clusters for the known metazoan "actinome" were used to identify putative new core actin regulators, together with a number of genes with conserved but poorly studied roles in the regulation of the actin cytoskeleton, several of which we studied in detail. This work suggests that although our search for new components of the core actin machinery is nearing saturation, regulation at the level of nuclear actin export, RNA splicing, ubiquitination, and other upstream processes remains an important but unexplored frontier of actin biology.
authors: MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, England, UK. j.rohn@ucl.ac.uk
authors: Jennifer L
authors: JL
authors: Rohn
authors: David
authors: D
authors: Sims
authors: Tao
authors: T
authors: Liu
authors: Marina
authors: M
authors: Fedorova
authors: Frieder
authors: F
authors: Schöck
authors: Joseph
authors: J
authors: Dopie
authors: Maria K
authors: MK
authors: Vartiainen
authors: Amy A
authors: AA
authors: Kiger
authors: Norbert
authors: N
authors: Perrimon
authors: Buzz
authors: B
authors: Baum
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002262:Carboxy-Lyases / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D048430:Cell Shape / Q000502:physiology; D016000:Cluster Analysis; D004247:DNA / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006434:Hemocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D008840:Microfilament Proteins / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D034622:RNA Interference; D012326:RNA Splicing / Q000502:physiology; D012330:RNA, Double-Stranded / Q000235:genetics / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000199:Actins; D002352:Carrier Proteins; D029721:Drosophila Proteins; C508978:Hyx protein, Drosophila; D008840:Microfilament Proteins; C479529:RBX1 protein, human; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D014404:Tubulin; D004247:DNA; D044843:SKP Cullin F-Box Protein Ligases; D020741:rho GTP-Binding Proteins; D002262:Carboxy-Lyases