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

Author

Listed:
  • Magnus E. Jakobsson

    (University of Oslo
    University of Copenhagen)

  • Jędrzej M. Małecki

    (University of Oslo)

  • Levon Halabelian

    (University of Toronto)

  • Benedikt S. Nilges

    (Max Planck Institute for Molecular Biomedicine
    University of Muenster)

  • Rita Pinto

    (University of Oslo)

  • Srikanth Kudithipudi

    (Stuttgart University)

  • Stephanie Munk

    (University of Copenhagen)

  • Erna Davydova

    (University of Oslo)

  • Fawzi R. Zuhairi

    (University of Oslo)

  • Cheryl H. Arrowsmith

    (University of Toronto)

  • Albert Jeltsch

    (Stuttgart University)

  • Sebastian A. Leidel

    (Max Planck Institute for Molecular Biomedicine
    University of Muenster)

  • Jesper V. Olsen

    (University of Copenhagen)

  • Pål Ø. Falnes

    (University of Oslo)

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.

Suggested Citation

  • 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, 2018. "The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05646-y
    DOI: 10.1038/s41467-018-05646-y
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    Cited by:

    1. Tanveer S. Batth & Jonas L. Simonsen & Cristina Hernández-Rollán & Søren Brander & Jens Preben Morth & Katja S. Johansen & Morten H. H. Nørholm & Jakob B. Hoof & Jesper V. Olsen, 2023. "A seven-transmembrane methyltransferase catalysing N-terminal histidine methylation of lytic polysaccharide monooxygenases," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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