1. Chromosomes and Gene Expression
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Stop codon context influences genome-wide stimulation of termination codon readthrough by aminoglycosides

  1. Jamie R Wangen
  2. Rachel Green  Is a corresponding author
  1. Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, United States
Research Article
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Cite this article as: eLife 2020;9:e52611 doi: 10.7554/eLife.52611

Abstract

Stop codon readthrough (SCR) occurs when the ribosome miscodes at a stop codon. Such readthrough events can be therapeutically desirable when a premature termination codon (PTC) is found in a critical gene. To study SCR in vivo in a genome-wide manner, we treated mammalian cells with aminoglycosides and performed ribosome profiling. We find that in addition to stimulating readthrough of PTCs, aminoglycosides stimulate readthrough of normal termination codons (NTCs) genome-wide. Stop codon identity, the nucleotide following the stop codon, and the surrounding mRNA sequence context all influence the likelihood of SCR. In comparison to NTCs, downstream stop codons in 3'UTRs are recognized less efficiently by ribosomes, suggesting that targeting of critical stop codons for readthrough may be achievable without general disruption of translation termination. Finally, we find that G418-induced miscoding alters gene expression with substantial effects on translation of histone genes, selenoprotein genes, and S-adenosylmethionine decarboxylase (AMD1).

Article and author information

Author details

  1. Jamie R Wangen

    Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7008-5749
  2. Rachel Green

    Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States
    For correspondence
    ragreen@jhmi.edu
    Competing interests
    Rachel Green, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9337-2003

Funding

Cystic Fibrosis Foundation (GREEN16G0)

  • Jamie R Wangen
  • Rachel Green

National Institutes of Health (T32 GM007445)

  • Jamie R Wangen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Nahum Sonenberg, McGill University, Canada

Publication history

  1. Received: October 9, 2019
  2. Accepted: January 22, 2020
  3. Accepted Manuscript published: January 23, 2020 (version 1)
  4. Version of Record published: March 23, 2020 (version 2)

Copyright

© 2020, Wangen & Green

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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