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

Research output: Contribution to journalJournal articlepeer-review

  • 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
  • Olsen, Jesper Velgaard
  • Pål Ø Falnes

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.

Original languageEnglish
Article number3411
JournalNature Communications
Volume9
Issue number1
ISSN2041-1723
DOIs
Publication statusPublished - 2018

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