Histone arginine demethylase JMJD6 is linked to stress granule assembly through demethylation of the stress granule-nucleating protein G3BP1

J Biol Chem. 2017 Nov 17;292(46):18886-18896. doi: 10.1074/jbc.M117.800706. Epub 2017 Sep 27.


Stress granules (SG) are membrane-less organelles that are condensates of stalled translation initiation complexes and mRNAs. SG formation is a cytoprotective response to environmental stress and results from protein interactions involving regions of low amino acid complexity and poorly defined post-translational modifications of SG components. Many RNA-binding proteins are methylated, and we previously demonstrated that the potent SG-nucleating protein G3BP1 is methylated by protein arginine methyltransferase 1 and 5 (PRMT1 and PRMT5). G3BP1 methylation represses SG formation and is reversible. Here we functionally link JMJD6 (Jumonji C domain-containing protein 6) to G3BP1 demethylation. Our findings reveal that JMJD6 is a novel SG component that interacts with G3BP1 complexes, and its expression reduces G3BP1 monomethylation and asymmetric dimethylation at three Arg residues. Knockdown of JMJD6 repressed SG formation and G3BP1 demethylation, but SG formation and G3BP1 demethylation were rescued with catalytically active but not mutant JMJD6. These results suggest that JMJD6 functions directly or indirectly as an arginine demethylase of G3BP1 that promotes SG formation.

Keywords: RNA-binding protein; demethylase; post-translational modification (PTM); protein methylation; stress granule; stress response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / metabolism
  • Cell Line
  • Cytoplasmic Granules / metabolism*
  • DNA Helicases / metabolism*
  • Demethylation
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Poly-ADP-Ribose Binding Proteins / metabolism*
  • Protein Interaction Maps
  • Protein Processing, Post-Translational
  • RNA Helicases / metabolism*
  • RNA Recognition Motif Proteins / metabolism*
  • Stress, Physiological


  • Poly-ADP-Ribose Binding Proteins
  • RNA Recognition Motif Proteins
  • Arginine
  • JMJD6 protein, human
  • Jumonji Domain-Containing Histone Demethylases
  • DNA Helicases
  • G3BP1 protein, human
  • RNA Helicases