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

Abstract:

: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.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Dopie J,Rajakylä EK,Joensuu MS,Huet G,Ferrantelli E,Xie T,Jäälinoja H,Jokitalo E,Vartiainen MK

doi

10.1242/jcs.169441

subject

Has Abstract

pub_date

2015-07-01 00:00:00

pages

2388-400

issue

13

eissn

0021-9533

issn

1477-9137

pii

jcs.169441

journal_volume

128

pub_type

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