Arginylation and methylation double up to regulate nuclear proteins and nuclear architecture in vivo

Chem Biol. 2011 Nov 23;18(11):1369-78. doi: 10.1016/j.chembiol.2011.08.019.

Abstract

Protein arginylation and arginine methylation are two posttranslational modifications of emerging importance that involve Arg residues and their modifications. To test a hypothesis that posttranslationally added arginines can be methylated, we used high-precision mass spectrometry and metabolic labeling to find whether posttranslationally added arginines can serve as methylation sites. We identified a number of proteins in vivo, on which posttranslationally added Arg have undergone mono- and dimethylation. This double modification predominantly affects the chromatin-containing nuclear fraction and likely plays an important regulatory role in chromatin-associated proteins. Moreover, inhibition of arginylation and Arg methylation results in a significant reduction of the nucleus size in cultured cells, suggesting changes in chromatin compaction and nuclear architecture. Our findings suggest a functional link between protein regulation by arginylation and methylation that affects nuclear structure in vivo.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aminoacyltransferases / antagonists & inhibitors
  • Aminoacyltransferases / genetics
  • Aminoacyltransferases / metabolism
  • Animals
  • Arginine / metabolism*
  • Cell Line
  • Cell Nucleus / metabolism
  • Cell Size
  • Chromatin / metabolism
  • Methylation
  • Mice
  • Naphthalenesulfonates / pharmacology
  • Nuclear Proteins / metabolism*
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Tandem Mass Spectrometry
  • Urea / analogs & derivatives
  • Urea / pharmacology

Substances

  • 7,7'-carbonylbis(azanediyl) bis(4-hydroxynaphthalene-2-sulfonic acid
  • Chromatin
  • Naphthalenesulfonates
  • Nuclear Proteins
  • Urea
  • Arginine
  • Aminoacyltransferases
  • arginyltransferase