title: Persistent nuclear actin filaments inhibit transcription by RNA polymerase II.
abstract: Actin is abundant in the nucleus and it is clear that nuclear actin has important functions. However, mystery surrounds the absence of classical actin filaments in the nucleus. To address this question, we investigated how polymerizing nuclear actin into persistent nuclear actin filaments affected transcription by RNA polymerase II. Nuclear filaments impaired nuclear actin dynamics by polymerizing and sequestering nuclear actin. Polymerizing actin into stable nuclear filaments disrupted the interaction of actin with RNA polymerase II and correlated with impaired RNA polymerase II localization, dynamics, gene recruitment, and reduced global transcription and cell proliferation. Polymerizing and crosslinking nuclear actin in vitro similarly disrupted the actin-RNA-polymerase-II interaction and inhibited transcription. These data rationalize the general absence of stable actin filaments in mammalian somatic nuclei. They also suggest a dynamic pool of nuclear actin is required for the proper localization and activity of RNA polymerase II.
authors: Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors: Leonid A
authors: LA
authors: Serebryannyy
authors: Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors: Megan
authors: M
authors: Parilla
authors: Laboratory of Fluorescence Dynamics, University of California Irvine, Irvine, CA 92697, USA.
authors: Paolo
authors: 0000-0003-3208-5347
authors: P
authors: Annibale
authors: Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors: Christina M
authors: CM
authors: Cruz
authors: Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA.
authors: Kyle
authors: K
authors: Laster
authors: Laboratory of Fluorescence Dynamics, University of California Irvine, Irvine, CA 92697, USA.
authors: Enrico
authors: 0000-0002-6450-7391
authors: E
authors: Gratton
authors: Department of Chemistry and Biochemistry, Ohio State University, Columbus, OH 43210, USA.
authors: Dmitri
authors: D
authors: Kudryashov
authors: Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA.
authors: Steven T
authors: ST
authors: Kosak
authors: Department of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors: Cara J
authors: 0000-0003-0912-7617
authors: CJ
authors: Gottardi
authors: Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA primal@uic.edu.
authors: Primal
authors: 0000-0001-8077-4273
authors: P
authors: de Lanerolle
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D003432:Cross-Linking Reagents / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D058105:Polymerization; D021381:Protein Transport; D012319:RNA Polymerase II / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000199:Actins; D003432:Cross-Linking Reagents; D012333:RNA, Messenger; D012319:RNA Polymerase II
keywords: Actin; Nuclear actin filaments; Nucleus; RNA polymerase II; Transcription