Arginine methylation of RNA helicase a determines its subcellular localization.
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.
Smith
Wendell A
WA
Division of Biological Sciences and University of California, San Diego Cancer Center, University of California, San Diego, La Jolla, California, 92093-0322, USA.
Schurter
Brandon T
BT
Wong-Staal
Flossie
F
David
Michael
M
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*
D001324:Autoantigens; D009363:Neoplasm Proteins; D001120:Arginine; C098487:DHX9 protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases