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Loss of N-terminal acetyltransferase A activity induces thermally unstable ribosomal proteins and increases their turnover in Saccharomyces cerevisiae

Author

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  • Ulises H. Guzman

    (University of Copenhagen)

  • Henriette Aksnes

    (University of Bergen)

  • Rasmus Ree

    (University of Bergen)

  • Nicolai Krogh

    (University of Copenhagen)

  • Magnus E. Jakobsson

    (University of Copenhagen
    Lund University)

  • Lars J. Jensen

    (University of Copenhagen)

  • Thomas Arnesen

    (University of Bergen
    University of Bergen
    Haukeland University Hospital)

  • Jesper V. Olsen

    (University of Copenhagen)

Abstract

Protein N-terminal (Nt) acetylation is one of the most abundant modifications in eukaryotes, covering ~50-80 % of the proteome, depending on species. Cells with defective Nt-acetylation display a wide array of phenotypes such as impaired growth, mating defects and increased stress sensitivity. However, the pleiotropic nature of these effects has hampered our understanding of the functional impact of protein Nt-acetylation. The main enzyme responsible for Nt-acetylation throughout the eukaryotic kingdom is the N-terminal acetyltransferase NatA. Here we employ a multi-dimensional proteomics approach to analyze Saccharomyces cerevisiae lacking NatA activity, which causes global proteome remodeling. Pulsed-SILAC experiments reveals that NatA-deficient strains consistently increase degradation of ribosomal proteins compared to wild type. Explaining this phenomenon, thermal proteome profiling uncovers decreased thermostability of ribosomes in NatA-knockouts. Our data are in agreement with a role for Nt-acetylation in promoting stability for parts of the proteome by enhancing the avidity of protein-protein interactions and folding.

Suggested Citation

  • Ulises H. Guzman & Henriette Aksnes & Rasmus Ree & Nicolai Krogh & Magnus E. Jakobsson & Lars J. Jensen & Thomas Arnesen & Jesper V. Olsen, 2023. "Loss of N-terminal acetyltransferase A activity induces thermally unstable ribosomal proteins and increases their turnover in Saccharomyces cerevisiae," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40224-x
    DOI: 10.1038/s41467-023-40224-x
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    1. Sylvia Varland & Rui Duarte Silva & Ine Kjosås & Alexandra Faustino & Annelies Bogaert & Maximilian Billmann & Hadi Boukhatmi & Barbara Kellen & Michael Costanzo & Adrian Drazic & Camilla Osberg & Kat, 2023. "N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity," Nature Communications, Nature, vol. 14(1), pages 1-27, December.
    2. Nina McTiernan & Ine Kjosås & Thomas Arnesen, 2025. "Illuminating the impact of N-terminal acetylation: from protein to physiology," Nature Communications, Nature, vol. 16(1), pages 1-15, December.

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