The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates

Research output: Contribution to journalArticle

Abstract

Eukaryotic elongation factor 1 alpha (eEF1A) delivers aminoacyl-tRNA to the ribosome and thereby plays a key role in protein synthesis. Human eEF1A is subject to extensive post-translational methylation, but several of the responsible enzymes remain unknown. Using a wide range of experimental approaches, we here show that human methyltransferase (MTase)-like protein 13 (METTL13) contains two distinct MTase domains targeting the N terminus and Lys55 of eEF1A, respectively. Our biochemical and structural analyses provide detailed mechanistic insights into recognition of the eEF1A N terminus by METTL13. Moreover, through ribosome profiling, we demonstrate that loss of METTL13 function alters translation dynamics and results in changed translation rates of specific codons. In summary, we here unravel the function of a human MTase, showing that it methylates eEF1A and modulates mRNA translation in a codon-specific manner.

Details

Authors
  • Magnus E Jakobsson
  • Jędrzej M Małecki
  • Levon Halabelian
  • Benedikt S Nilges
  • Rita Pinto
  • Srikanth Kudithipudi
  • Stephanie Munk
  • Erna Davydova
  • Fawzi R Zuhairi
  • Cheryl H Arrowsmith
  • Albert Jeltsch
  • Sebastian A Leidel
  • Jesper V Olsen
  • Pål Ø Falnes
External organisations
  • University of Oslo
  • University of Copenhagen
  • University of Münster
  • University of Stuttgart
  • University of Toronto
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biochemistry and Molecular Biology

Keywords

  • Codon/genetics, Humans, Methyltransferases/chemistry, Peptide Elongation Factor 1/chemistry, Protein Binding, Protein Processing, Post-Translational, RNA, Messenger/metabolism, Ribosomes/metabolism
Original languageEnglish
Pages (from-to)3411
JournalNature Communications
Volume9
Issue number1
Publication statusPublished - 2018 Aug 24
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes