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Publication : Genome-wide RNAi screen for nuclear actin reveals a network of cofilin regulators.

First Author  Dopie J Year  2015
Journal  J Cell Sci Volume  128
Issue  13 Pages  2388-400
PubMed ID  26021350 Mgi Jnum  J:236948
Mgi Id  MGI:5810251 Doi  10.1242/jcs.169441
Citation  Dopie J, et al. (2015) Genome-wide RNAi screen for nuclear actin reveals a network of cofilin regulators. J Cell Sci 128(13):2388-400
abstractText  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), SNF4Agamma (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.
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