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Genetic regulation of post-translational modification of two distinct proteins

Author

Listed:
  • Arianna Landini

    (University of Edinburgh)

  • Irena Trbojević-Akmačić

    (Genos Glycoscience Research Laboratory)

  • Pau Navarro

    (University of Edinburgh)

  • Yakov A. Tsepilov

    (Laboratory of Glycogenomics, Institute of Cytology and Genetics
    Novosibirsk State University)

  • Sodbo Z. Sharapov

    (Laboratory of Glycogenomics, Institute of Cytology and Genetics)

  • Frano Vučković

    (Genos Glycoscience Research Laboratory)

  • Ozren Polašek

    (School of Medicine, University of Split
    Algebra University College)

  • Caroline Hayward

    (University of Edinburgh)

  • Tea Petrović

    (Genos Glycoscience Research Laboratory)

  • Marija Vilaj

    (Genos Glycoscience Research Laboratory)

  • Yurii S. Aulchenko

    (Laboratory of Glycogenomics, Institute of Cytology and Genetics)

  • Gordan Lauc

    (Genos Glycoscience Research Laboratory
    University of Zagreb)

  • James F. Wilson

    (University of Edinburgh
    University of Edinburgh)

  • Lucija Klarić

    (University of Edinburgh)

Abstract

Post-translational modifications diversify protein functions and dynamically coordinate their signalling networks, influencing most aspects of cell physiology. Nevertheless, their genetic regulation or influence on complex traits is not fully understood. Here, we compare the genetic regulation of the same PTM of two proteins – glycosylation of transferrin and immunoglobulin G (IgG). By performing genome-wide association analysis of transferrin glycosylation, we identify 10 significantly associated loci, 9 of which were not reported previously. Comparing these with IgG glycosylation-associated genes, we note protein-specific associations with genes encoding glycosylation enzymes (transferrin - MGAT5, ST3GAL4, B3GAT1; IgG - MGAT3, ST6GAL1), as well as shared associations (FUT6, FUT8). Colocalisation analyses of the latter suggest that different causal variants in the FUT genes regulate fucosylation of the two proteins. Glycosylation of these proteins is thus genetically regulated by both shared and protein-specific mechanisms.

Suggested Citation

  • Arianna Landini & Irena Trbojević-Akmačić & Pau Navarro & Yakov A. Tsepilov & Sodbo Z. Sharapov & Frano Vučković & Ozren Polašek & Caroline Hayward & Tea Petrović & Marija Vilaj & Yurii S. Aulchenko &, 2022. "Genetic regulation of post-translational modification of two distinct proteins," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29189-5
    DOI: 10.1038/s41467-022-29189-5
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