IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-24076-x.html
   My bibliography  Save this article

Repurposing tRNAs for nonsense suppression

Author

Listed:
  • Suki Albers

    (Institute of Biochemistry and Molecular Biology, University of Hamburg)

  • Bertrand Beckert

    (Institute of Biochemistry and Molecular Biology, University of Hamburg)

  • Marco C. Matthies

    (Center for Bioinformatics, University of Hamburg)

  • Chandra Sekhar Mandava

    (Uppsala University)

  • Raphael Schuster

    (Institute of Organic Chemistry, University of Hamburg)

  • Carolin Seuring

    (Center for Structural and Systems Biology)

  • Maria Riedner

    (Institute of Organic Chemistry, University of Hamburg)

  • Suparna Sanyal

    (Uppsala University)

  • Andrew E. Torda

    (Center for Bioinformatics, University of Hamburg)

  • Daniel N. Wilson

    (Institute of Biochemistry and Molecular Biology, University of Hamburg)

  • Zoya Ignatova

    (Institute of Biochemistry and Molecular Biology, University of Hamburg)

Abstract

Three stop codons (UAA, UAG and UGA) terminate protein synthesis and are almost exclusively recognized by release factors. Here, we design de novo transfer RNAs (tRNAs) that efficiently decode UGA stop codons in Escherichia coli. The tRNA designs harness various functionally conserved aspects of sense-codon decoding tRNAs. Optimization within the TΨC-stem to stabilize binding to the elongation factor, displays the most potent effect in enhancing suppression activity. We determine the structure of the ribosome in a complex with the designed tRNA bound to a UGA stop codon in the A site at 2.9 Å resolution. In the context of the suppressor tRNA, the conformation of the UGA codon resembles that of a sense-codon rather than when canonical translation termination release factors are bound, suggesting conformational flexibility of the stop codons dependent on the nature of the A-site ligand. The systematic analysis, combined with structural insights, provides a rationale for targeted repurposing of tRNAs to correct devastating nonsense mutations that introduce a premature stop codon.

Suggested Citation

  • Suki Albers & Bertrand Beckert & Marco C. Matthies & Chandra Sekhar Mandava & Raphael Schuster & Carolin Seuring & Maria Riedner & Suparna Sanyal & Andrew E. Torda & Daniel N. Wilson & Zoya Ignatova, 2021. "Repurposing tRNAs for nonsense suppression," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24076-x
    DOI: 10.1038/s41467-021-24076-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-24076-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-24076-x?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Nikhil Bharti & Leonardo Santos & Marcos Davyt & Stine Behrmann & Marie Eichholtz & Alejandro Jimenez-Sanchez & Jeong S. Hong & Andras Rab & Eric J. Sorscher & Suki Albers & Zoya Ignatova, 2024. "Translation velocity determines the efficacy of engineered suppressor tRNAs on pathogenic nonsense mutations," Nature Communications, Nature, vol. 15(1), pages 1-10, December.

    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:12:y:2021:i:1:d:10.1038_s41467-021-24076-x. 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.