Regulated Ire1-dependent mRNA decay requires no-go mRNA degradation to maintain endoplasmic reticulum homeostasis in S. pombe
- Johns Hopkins School of Medicine, United States
- University of California, San Francisco, United States
Abstract
The unfolded protein response (UPR) monitors and adjusts the protein folding capacity of the endoplasmic reticulum (ER). In S. pombe, the ER membrane-resident kinase/endoribonuclease Ire1 utilizes a mechanism of selective degradation of ER-bound mRNAs (RIDD) to maintain homeostasis. We used a genetic screen to identify factors critical to the Ire1-mediated UPR and found several proteins, Dom34, Hbs1 and Ski complex subunits, previously implicated in ribosome rescue and mRNA no-go-decay (NGD). Ribosome profiling in ER-stressed cells lacking these factors revealed that Ire1-mediated cleavage of ER-associated mRNAs results in ribosome stalling and mRNA degradation. Stalled ribosomes iteratively served as a ruler to template precise, regularly spaced upstream mRNA cleavage events. This clear signature uncovered hundreds of novel target mRNAs. Our results reveal that the UPR in S. pombe executes RIDD in an intricate interplay between Ire1, translation, and the NGD pathway, and establish a critical role for NGD in maintaining ER homeostasis.
Data availability
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Regulated Ire1-dependent mRNA decay requires no-go mRNA degradation to maintain endoplasmic reticulum homeostasis in S. pombePublicly available at the NCBI Gene Expression Omnibus (accession no: GSE98934).
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The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasisPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE40298).
Article and author information
Author details
Funding
Howard Hughes Medical Institute
- Peter Walter
- Rachel Green
National Institute of General Medical Sciences (GM 059425)
- Rachel Green
National Institutes of Health
- Peter Walter
National Institute of Diabetes and Digestive and Kidney Diseases
- Nicholas R Guydosh
Human Frontier Science Program
- Phillip Kimmig
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Guydosh et al.
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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Regulated Ire1-dependent mRNA decay requires no-go mRNA degradation to maintain endoplasmic reticulum homeostasis in S. pombe
eLife 6:e29216.
https://doi.org/10.7554/eLife.29216
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