IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-15796-7.html
   My bibliography  Save this article

Perturbing proteomes at single residue resolution using base editing

Author

Listed:
  • Philippe C. Després

    (Microbiologie et Bio-informatique, Faculté de Sciences et Génie, Université Laval
    PROTEO, le regroupement québécois de recherche sur la fonction, l’ingénierie et les applications des protéines, Université Laval
    Centre de Recherche en Données Massives (CRDM), Université Laval
    Institut de Biologie Intégrative et des Systèmes, Université Laval)

  • Alexandre K. Dubé

    (Microbiologie et Bio-informatique, Faculté de Sciences et Génie, Université Laval
    PROTEO, le regroupement québécois de recherche sur la fonction, l’ingénierie et les applications des protéines, Université Laval
    Centre de Recherche en Données Massives (CRDM), Université Laval
    Institut de Biologie Intégrative et des Systèmes, Université Laval)

  • Motoaki Seki

    (University of Tokyo, Tokyo)

  • Nozomu Yachie

    (University of Tokyo, Tokyo
    Graduate School of Science, the University of Tokyo
    Institute for Advanced Biosciences, Keio University)

  • Christian R. Landry

    (Microbiologie et Bio-informatique, Faculté de Sciences et Génie, Université Laval
    PROTEO, le regroupement québécois de recherche sur la fonction, l’ingénierie et les applications des protéines, Université Laval
    Centre de Recherche en Données Massives (CRDM), Université Laval
    Institut de Biologie Intégrative et des Systèmes, Université Laval)

Abstract

Base editors derived from CRISPR-Cas9 systems and DNA editing enzymes offer an unprecedented opportunity for the precise modification of genes, but have yet to be used at a genome-scale throughput. Here, we test the ability of the Target-AID base editor to systematically modify genes genome-wide by targeting yeast essential genes. We mutate around 17,000 individual sites in parallel across more than 1500 genes. We identify over 700 sites at which mutations have a significant impact on fitness. Using previously determined and preferred Target-AID mutational outcomes, we find that gRNAs with significant effects on fitness are enriched in variants predicted to be deleterious based on residue conservation and predicted protein destabilization. We identify key features influencing effective gRNAs in the context of base editing. Our results show that base editing is a powerful tool to identify key amino acid residues at the scale of proteomes.

Suggested Citation

  • Philippe C. Després & Alexandre K. Dubé & Motoaki Seki & Nozomu Yachie & Christian R. Landry, 2020. "Perturbing proteomes at single residue resolution using base editing," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15796-7
    DOI: 10.1038/s41467-020-15796-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-15796-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-15796-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15796-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.