title: Arginine methylation of RNA helicase a determines its subcellular localization.
abstract: RNA helicase A (RHA) undergoes nuclear translocation via a classical import mechanism utilizing karyopherin beta. The nuclear transport domain (NTD) of RHA is known to be necessary and sufficient for its bi-directional nuclear trafficking. We report here that arginine methylation is a novel requirement for NTD-mediated nuclear import. Nuclear translocation of glutathione S-transferase (GST)-NTD fusion proteins is abrogated by arginine-methylation inhibitors. However, in vitro arginine-methylation of GST-NTD prior to injection allows the fusion protein to localize to the nucleus in the presence of methylation inhibitors. Removal of the arginine-rich C-terminal region negates the effects of the methylation inhibitors on NTD import, suggesting that methylation of the NTD C terminus the relieves the cytoplasmic retention of RHA. The NTD physically interacts with PRMT1, the major protein arginine methyltransferase. These findings provide evidence for a novel arginine methylation-dependent regulatory pathway controlling the nuclear import of RHA.
authors.affiliation: Division of Biological Sciences and University of California, San Diego Cancer Center, University of California, San Diego, La Jolla, California, 92093-0322, USA.
authors.forename: Wendell A
authors.initials: WA
authors.lastname: Smith
authors.forename: Brandon T
authors.initials: BT
authors.lastname: Schurter
authors.forename: Flossie
authors.initials: F
authors.lastname: Wong-Staal
authors.forename: Michael
authors.initials: M
authors.lastname: David
mesh_terms: D001120:Arginine / Q000378:metabolism; D001324:Autoantigens / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D053487:DEAD-box RNA Helicases; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology; D008745:Methylation; D009363:Neoplasm Proteins; D021381:Protein Transport; D020365:RNA Helicases / Q000378:metabolism*
chemical_list: D001324:Autoantigens; D009363:Neoplasm Proteins; D001120:Arginine; C098487:DHX9 protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases