TY - JOUR T1 - Genome-wide RNAi screen for nuclear actin reveals a network of cofilin regulators. JF - J Cell Sci Y1 - 2015 A1 - Dopie, Joseph A1 - Rajakylä, Eeva K A1 - Joensuu, Merja S A1 - Huet, Guillaume A1 - Ferrantelli, Evelina A1 - Xie, Tiao A1 - Jäälinoja, Harri A1 - Jokitalo, Eija A1 - Vartiainen, Maria K KW - Actin Depolymerizing Factors KW - Actins KW - Animals KW - Cell Nucleus KW - Conserved Sequence KW - drosophila melanogaster KW - Drosophila Proteins KW - Evolution, Molecular KW - Genetic Testing KW - genome KW - Mice KW - Models, Biological KW - Nerve Tissue Proteins KW - Phosphorylation KW - Polymerization KW - Protein-Serine-Threonine Kinases KW - RNA Interference AB -

Nuclear actin plays an important role in many processes that regulate gene expression. Cytoplasmic actin dynamics are tightly controlled by numerous actin-binding proteins, but regulation of nuclear actin has remained unclear. Here, we performed a genome-wide RNA interference (RNAi) screen in Drosophila cells to identify proteins that influence either nuclear polymerization or import of actin. We validate 19 factors as specific hits, and show that Chinmo (known as Bach2 in mammals), SNF4Aγ (Prkag1 in mammals) and Rab18 play a role in nuclear localization of actin in both fly and mammalian cells. We identify several new regulators of cofilin activity, and characterize modulators of both cofilin kinases and phosphatase. For example, Chinmo/Bach2, which regulates nuclear actin levels also in vivo, maintains active cofilin by repressing the expression of the kinase Cdi (Tesk in mammals). Finally, we show that Nup98 and lamin are candidates for regulating nuclear actin polymerization. Our screen therefore reveals new aspects of actin regulation and links nuclear actin to many cellular processes.

VL - 128 IS - 13 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26021350?dopt=Abstract ER -