Arginine methylation of RNA helicase a determines its subcellular localization

J Biol Chem. 2004 May 28;279(22):22795-8. doi: 10.1074/jbc.C300512200. Epub 2004 Apr 14.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Arginine / metabolism
  • Autoantigens / metabolism*
  • Cell Nucleus / metabolism
  • DEAD-box RNA Helicases
  • Humans
  • Lupus Erythematosus, Systemic / enzymology
  • Methylation
  • Neoplasm Proteins
  • Protein Transport
  • RNA Helicases / metabolism*

Substances

  • Autoantigens
  • Neoplasm Proteins
  • Arginine
  • DHX9 protein, human
  • DEAD-box RNA Helicases
  • RNA Helicases