2. Academic Validation
  3. The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates

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

  • Nat Commun. 2018 Aug 24;9(1):3411. doi: 10.1038/s41467-018-05646-y.
Magnus E Jakobsson 1 2,  Jędrzej M Małecki 3,  Levon Halabelian 4,  Benedikt S Nilges 5 6,  Rita Pinto 3,  Srikanth Kudithipudi 7,  Stephanie Munk 8,  Erna Davydova 3,  Fawzi R Zuhairi 3,  Cheryl H Arrowsmith 4,  Albert Jeltsch 7,  Sebastian A Leidel 5 6,  Jesper V Olsen 9,  Pål Ø Falnes 10
Affiliations

Affiliations

  • 1 Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, 0316, Oslo, Norway. [email protected].
  • 2 Proteomics Program, Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Protein Research (NNF-CPR), University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark. [email protected].
  • 3 Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, 0316, Oslo, Norway.
  • 4 Structural Genomics Consortium, and Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, M5G 2M9, Canada.
  • 5 Max Planck Research Group for RNA Biology, Max Planck Institute for Molecular Biomedicine, 48149, Muenster, Germany.
  • 6 Cells-in-Motion Cluster of Excellence, University of Muenster, 48149, Muenster, Germany.
  • 7 Department of Biochemistry, Institute of Biochemistry and Technical Biochemistry, Stuttgart University, Allmandring 31, 70569, Stuttgart, Germany.
  • 8 Proteomics Program, Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Protein Research (NNF-CPR), University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.
  • 9 Proteomics Program, Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Protein Research (NNF-CPR), University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark. [email protected].
  • 10 Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, 0316, Oslo, Norway. [email protected].
PMID: 30143613 DOI: 10.1038/s41467-018-05646-y
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.

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