Methylation of ribosomal protein S10 by protein-arginine methyltransferase 5 regulates ribosome biogenesis

J Biol Chem. 2010 Apr 23;285(17):12695-705. doi: 10.1074/jbc.M110.103911. Epub 2010 Feb 16.

Abstract

Modulation of ribosomal assembly is a fine tuning mechanism for cell number and organ size control. Many ribosomal proteins undergo post-translational modification, but their exact roles remain elusive. Here, we report that ribosomal protein s10 (RPS10) is a novel substrate of an oncoprotein, protein-arginine methyltransferase 5 (PRMT5). We show that PRMT5 interacts with RPS10 and catalyzes its methylation at the Arg(158) and Arg(160) residues. The methylation of RPS10 at Arg(158) and Arg(160) plays a role in the proper assembly of ribosomes, protein synthesis, and optimal cell proliferation. The RPS10-R158K/R160K mutant is not efficiently assembled into ribosomes and is unstable and prone to degradation by the proteasomal pathway. In nucleoli, RPS10 interacts with nucleophosmin/B23 and is predominantly concentrated in the granular component region, which is required for ribosome assembly. The RPS10 methylation mutant interacts weakly with nucleophosmin/B23 and fails to concentrate in the granular component region. Our results suggest that PRMT5 is likely to regulate cell proliferation through the methylation of ribosome proteins, and thus reveal a novel mechanism for PRMT5 in tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Catalysis
  • Cell Line
  • Cell Proliferation
  • Humans
  • Methylation
  • Mutation, Missense
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nucleophosmin
  • Protein Biosynthesis / physiology*
  • Protein Methyltransferases / genetics
  • Protein Methyltransferases / metabolism*
  • Protein-Arginine N-Methyltransferases
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism*
  • Ribosomes / genetics
  • Ribosomes / metabolism*

Substances

  • NPM1 protein, human
  • Nuclear Proteins
  • RPS10 protein, human
  • Ribosomal Proteins
  • ribosomal protein S10
  • Nucleophosmin
  • Protein Methyltransferases
  • PRMT5 protein, human
  • Protein-Arginine N-Methyltransferases