Nonsense mRNA suppression via nonstop decay

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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.

Data availability

The following data sets were generated

1. Joshua Arribere
2. Andrew Fire
(2017) Nonsense-mediated decay triggers nonstop mRNA decay in a metazoan
SRP115527.

ftp://ftp-trace.ncbi.nlm.nih.gov/sra/review/SRP115527_20170817_075839_ffa243f771800363714f6055d9236fd6

Article and author information

Author details

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.

"This ORCID iD identifies the author of this article:" 0000-0002-2467-7791
Andrew Z Fire

Department of Pathology, Stanford University School of Medicine, Stanford, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 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.

Copyright

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.