Non-invasive measurement of mRNA decay reveals translation initiation as the major determinant of mRNA stability
- University of California, Berkeley, United States
- ETH Zurich, Switzerland
Abstract
The cytoplasmic abundance of mRNAs is strictly controlled through a balance of production and degradation. Whereas the control of mRNA synthesis through transcription has been well characterized, less is known about the regulation of mRNA turnover, and a consensus model explaining the wide variations in mRNA decay rates remains elusive. Here, we combine non-invasive transcriptome-wide mRNA production and stability measurements with selective and acute perturbations to demonstrate that mRNA degradation is tightly coupled to the regulation of translation, and that a competition between translation initiation and mRNA decay -but not codon optimality or elongation- is the major determinant of mRNA stability in yeast. Our refined measurements also reveal a remarkably dynamic transcriptome with an average mRNA half-life of only 4.8 minutes - much shorter than previously thought. Furthermore, global mRNA destabilization by inhibition of translation initiation induces a dose-dependent formation of processing bodies in which mRNAs can decay over time.
Data availability
Sequencing data have been deposited in GEO under accession code GSE119560.
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mRNA stability as measured by thiouracil incorporation in the presence and absence of translational inhibitorsublicly available at the NCBI Gene Expression Omnibus (accession no: GSE119560).
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translational efficiencyGEO accession number: GSE34082.
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Cramer (2) mRNA halflifePublicly available.
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Peltz mRNA halflifeSupplementary Tables S1, S2, and S3 (Publicly available).
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Coller (1) and (2) mRNA halflifeTable S1 (Publicly available).
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Struhl mRNA stabilityTable S2 (Publicly available).
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Pipel mRNA stabilitySupplementary Table 1 (Publicly available).
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Weis (1) mRNA stabilitySupplemental Data (Publicly available).
Article and author information
Author details
Christopher F Mugler
Stephanie Heinrich
Funding
National Institutes of Health
- Leon Y Chan
- Christopher F Mugler
- Karsten Weis
Damon Runyon Cancer Research Foundation
- Leon Y Chan
Shurl and Kay Curci Foundation
- Leon Y Chan
European Molecular Biology Organization
- Stephanie Heinrich
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Stephanie Heinrich
- Pascal Vallotton
- Karsten Weis
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Chan 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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Non-invasive measurement of mRNA decay reveals translation initiation as the major determinant of mRNA stability
eLife 7:e32536.
https://doi.org/10.7554/eLife.32536
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