title: Facioscapulohumeral muscular dystrophy region gene 1 is a dynamic RNA-associated and actin-bundling protein.
abstract: FSHD region gene 1 (FRG1) is a dynamic nuclear and cytoplasmic protein that, in skeletal muscle, shows additional localization to the sarcomere. Maintaining appropriate levels of FRG1 protein is critical for muscular and vascular development in vertebrates; however, its precise molecular function is unknown. This study investigates the molecular functions of human FRG1, along with mouse FRG1 and Xenopus frg1, using molecular, biochemical, and cellular-biological approaches, to provide further insight into its roles in vertebrate development. The nuclear fraction of the endogenous FRG1 is localized in nucleoli, Cajal bodies, and actively transcribed chromatin; however, contrary to overexpressed FRG1, the endogenous FRG1 is not associated with nuclear speckles. We characterize the nuclear and nucleolar import of FRG1, the potential effect of phosphorylation, and its interaction with the importin karyopherin α2. Consistent with a role in RNA biogenesis, human FRG1 is associated with mRNA in vivo and invitro, interacts directly with TAP (Tip-associated protein; the major mRNA export receptor), and is a dynamic nuclear-cytoplasmic shuttling protein supporting a function for FRG1 in mRNA transport. Biochemically, we characterize FRG1 actin binding activity and show that the cytoplasmic pool of FRG1 is dependent on an intact actin cytoskeleton for its localization. These data provide the first biochemical activities (actin binding and RNA binding) for human FRG1 and the characterization of the endogenous human FRG1, together indicating that FRG1 is involved in multiple aspects of RNA biogenesis, including mRNA transport and, potentially, cytoplasmic mRNA localization.
authors.affiliation: B107 Chemical and Life Sciences Laboratory, Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601 South Goodwin Avenue, Urbana, IL 61801, USA.
authors.forename: Chia-Yun Jessica
authors.initials: CY
authors.lastname: Sun
authors.forename: Silvana
authors.initials: S
authors.lastname: van Koningsbruggen
authors.forename: Steven W
authors.initials: SW
authors.lastname: Long
authors.forename: Kirsten
authors.initials: K
authors.lastname: Straasheijm
authors.forename: Rinse
authors.initials: R
authors.lastname: Klooster
authors.forename: Takako I
authors.initials: TI
authors.lastname: Jones
authors.forename: Michel
authors.initials: M
authors.lastname: Bellini
authors.forename: Lyne
authors.initials: L
authors.lastname: Levesque
authors.forename: William M
authors.initials: WM
authors.lastname: Brieher
authors.forename: Silvère M
authors.initials: SM
authors.lastname: van der Maarel
authors.forename: Peter L
authors.initials: PL
authors.lastname: Jones
mesh_terms: D000199:Actins / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D002466:Cell Nucleolus / Q000737:chemistry; D002467:Cell Nucleus / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins; D014981:Xenopus; D029867:Xenopus Proteins / Q000378:metabolism
chemical_list: D000199:Actins; C543102:FRG1 protein, Xenopus; C101270:FRG1 protein, human; C484440:Frg1 protein, mouse; D028884:Karyopherins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029867:Xenopus Proteins