SET7/9 interacts and methylates the ribosomal protein, eL42 and regulates protein synthesis

Biochim Biophys Acta Mol Cell Res. 2020 Feb;1867(2):118611. doi: 10.1016/j.bbamcr.2019.118611. Epub 2019 Nov 19.

Abstract

Methylation of proteins is emerging to be an important regulator of protein function. SET7/9, a protein lysine methyltransferase, catalyses methylation of several proteins involved in diverse biological processes. SET7/9-mediated methylation often regulates the stability, sub-cellular localization and protein-protein interactions of its substrate proteins. Here, we aimed to identify novel biological processes regulated by SET7/9 by identifying new interaction partners. For this we used yeast two-hybrid screening and identified the large subunit ribosomal protein, eL42 as a potential interactor of SET7/9. We confirmed the SET7/9-eL42 interaction by co-immunoprecipitation and GST pulldown studies. The N-terminal MORN domain of SET7/9 is essential for its interaction with eL42. Importantly, we identified that SET7/9 methylates eL42 at three different lysines - Lys53, Lys80 and Lys100 through site-directed mutagenesis. By puromycin incorporation assay, we find that SET7/9-mediated methylation of eL42 affects global translation. This study identifies a new role of the functionally versatile SET7/9 lysine methyltransferase in the regulation of global protein synthesis.

Keywords: Lysine methylation; Protein-protein interaction; RPL36A; SETD7; Translation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • HEK293 Cells
  • Histone-Lysine N-Methyltransferase / antagonists & inhibitors
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Humans
  • Lysine / chemistry
  • Methylation
  • Protein Biosynthesis
  • Protein Domains
  • Protein Interaction Domains and Motifs
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Ribosomal Proteins / chemistry
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism*
  • Two-Hybrid System Techniques

Substances

  • Protein Subunits
  • RNA, Small Interfering
  • RPL36A protein, human
  • Ribosomal Proteins
  • Histone-Lysine N-Methyltransferase
  • SETD7 protein, human
  • Lysine