Dynamics of human protein arginine methyltransferase 1(PRMT1) in vivo

J Biol Chem. 2005 Nov 11;280(45):38005-10. doi: 10.1074/jbc.M502458200. Epub 2005 Sep 13.

Abstract

Arginine methylation is a posttranslational protein modification catalyzed by a family of protein arginine methyltransferases (PRMT), the predominant member of which is PRMT1. Despite its major role in arginine methylation of nuclear proteins, surprisingly little is known about the subcellular localization and dynamics of PRMT1. We show here that only a fraction of PRMT1 is located in the nucleus, but the protein is predominantly cytoplasmic. Fluorescence recovery after photobleaching experiments reveal that PRMT1 is highly mobile both in the cytoplasm and the nucleus. However, inhibition of methylation leads to a significant nuclear accumulation of PRMT1, concomitant with the appearance of an immobile fraction of the protein in the nucleus, but not the cytoplasm. Both the accumulation and immobility of PRMT1 is reversed when re-methylation is allowed, suggesting a mechanism where PRMT1 is trapped by unmethylated substrates such as core histones and heterogeneous nuclear ribonucleoprotein proteins until it has executed the methylation reaction.

Publication types

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

MeSH terms

  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Cytoplasm / metabolism
  • Endothelial Cells / cytology
  • Humans
  • Methylation
  • Nuclear Proteins / metabolism
  • Protein Transport
  • Protein-Arginine N-Methyltransferases / genetics
  • Protein-Arginine N-Methyltransferases / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*

Substances

  • Nuclear Proteins
  • Repressor Proteins
  • PRMT1 protein, human
  • PRMT6 protein, human
  • Protein-Arginine N-Methyltransferases