1. Genes and Chromosomes
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Nonsense mRNA suppression via nonstop decay

  1. Joshua A Arribere Is a corresponding author
  2. Andrew Z Fire
  1. University of California, Santa Cruz, United States
  2. Stanford University School of Medicine, United States
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Cite as: eLife 2018;7:e33292 doi: 10.7554/eLife.33292

Abstract

Nonsense-mediated mRNA decay is the process by which mRNAs bearing premature stop codons are recognized and cleared from the cell. While considerable information has accumulated regarding recognition of the premature stop codon, less is known about the ensuing mRNA suppression. During the characterization of a second, distinct translational surveillance pathway (nonstop mRNA decay), we trapped intermediates in nonsense mRNA degradation. We present data in support of a model wherein nonsense-mediated decay funnels into the nonstop decay pathway in C. elegans. Specifically, our results point to SKI-exosome decay and pelota-based ribosome removal as key steps facilitating suppression and clearance of prematurely-terminated translation complexes. These results suggest a model in which premature stop codons elicit nucleolytic cleavage, with the nonstop pathway disengaging ribosomes and degrading the resultant RNA fragments to suppress ongoing expression.

Article and author information

Author details

  1. Joshua A Arribere

    Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, United States
    For correspondence
    jarriber@ucsc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-2467-7791
  2. Andrew Z Fire

    Department of Pathology, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0001-6217-8312

Funding

National Institutes of Health (R01GM37706)

  • Andrew Z Fire

National Institutes of Health (5F32GM112474-02)

  • Joshua A Arribere

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

Reviewing Editor

  1. Rachel Green, Reviewing Editor, Johns Hopkins School of Medicine, United States

Publication history

  1. Received: November 2, 2017
  2. Accepted: January 5, 2018
  3. Accepted Manuscript published: January 8, 2018 (version 1)

Copyright

© 2018, Arribere & Fire

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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