Arginine Demethylation of G3BP1 Promotes Stress Granule Assembly

J Biol Chem. 2016 Oct 21;291(43):22671-22685. doi: 10.1074/jbc.M116.739573. Epub 2016 Sep 6.


Stress granules (SGs) are cytoplasmic condensates of stalled messenger ribonucleoprotein complexes (mRNPs) that form when eukaryotic cells encounter environmental stress. RNA-binding proteins are enriched for arginine methylation and facilitate SG assembly through interactions involving regions of low amino acid complexity. How methylation of specific RNA-binding proteins regulates RNA granule assembly has not been characterized. Here, we examined the potent SG-nucleating protein Ras-GAP SH3-binding protein 1 (G3BP1), and found that G3BP1 is differentially methylated on specific arginine residues by protein arginine methyltransferase (PRMT) 1 and PRMT5 in its RGG domain. Several genetic and biochemical interventions that increased methylation repressed SG assembly, whereas interventions that decreased methylation promoted SG assembly. Arsenite stress quickly and reversibly decreased asymmetric arginine methylation on G3BP1. These data indicate that arginine methylation in the RGG domain prevents large SG assembly and rapid demethylation is a novel signal that regulates SG formation.

Keywords: G3BP1; RNA binding protein; mRNA; post-translational modification (PTM); protein arginine N-methyltransferase (PRMT); protein arginine N-methyltransferase 5 (PRMT5); stress granule.

MeSH terms

  • Arginine / genetics
  • Arginine / metabolism
  • Arsenites / pharmacology*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cytoplasmic Granules / genetics
  • Cytoplasmic Granules / metabolism*
  • DNA Helicases
  • Humans
  • Methylation
  • Poly-ADP-Ribose Binding Proteins
  • Protein-Arginine N-Methyltransferases / genetics
  • Protein-Arginine N-Methyltransferases / metabolism
  • RNA Helicases
  • RNA Recognition Motif Proteins
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Stress, Physiological / drug effects*


  • Arsenites
  • Carrier Proteins
  • Poly-ADP-Ribose Binding Proteins
  • RNA Recognition Motif Proteins
  • Repressor Proteins
  • Arginine
  • PRMT1 protein, human
  • PRMT5 protein, human
  • Protein-Arginine N-Methyltransferases
  • DNA Helicases
  • G3BP1 protein, human
  • RNA Helicases
  • arsenite