Facioscapulohumeral muscular dystrophy region gene 1 Is a dynamic RNA-associated and actin-bundling protein

Chia Yun Jessica Sun, Silvana Van Koningsbruggen, Steven W. Long, Kirsten Straasheijm, Rinse Klooster, Takako I. Jones, Michel Bellini, Lyne Levesque, William M. Brieher, Silvère M. Van Der Maarel, Peter L. Jones

Research output: Contribution to journalArticlepeer-review


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 in vitro, 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.

Original languageEnglish (US)
Pages (from-to)397-416
Number of pages20
JournalJournal of Molecular Biology
Issue number2
StatePublished - Aug 12 2011


  • TAP
  • actin binding
  • karyopherin α2
  • mRNA transport
  • nucleolus

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


Dive into the research topics of 'Facioscapulohumeral muscular dystrophy region gene 1 Is a dynamic RNA-associated and actin-bundling protein'. Together they form a unique fingerprint.

Cite this