Cis -regulatory elements explain most of the mRNA stability variation across genes in yeast
Open accessPublished version of a preprint
Abstract
The stability of mRNA is one of the major determinants of gene expression. Although a wealth of sequence elements regulating mRNA stability has been described, their quantitative contributions to half-life are unknown. Here, we built a quantitative model for Saccharomyces cerevisiae based on functional mRNA sequence features that explains 59% of the half-life variation between genes and predicts half-life at a median relative error of 30%. The model revealed a new destabilizing 3′ UTR motif, ATATTC, which we functionally validated. Codon usage proves to be the major determinant of mRNA stability. Nonetheless, single-nucleotide variations have the largest effect when occurring on 3′ UTR motifs or upstream AUGs. Analyzing mRNA half-life data of 34 knockout strains showed that the effect of codon usage not only requires functional decapping and deadenylation, but also the 5′-to-3′ exonuclease Xrn1, the nonsense-mediated decay genes, but not no-go decay. Altogether, this study quantitatively delineates the contributions of mRNA sequence features on stability in yeast, reveals their functional dependencies on degradation pathways, and allows accurate prediction of half-life from mRNA sequence.
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- Authors
- Cheng, J., Maier, K. C., Avsec, Ž., Rus, P., & Gagneur, J.
- Affiliations
- Technical University of Munich (DE)
- Max Planck Institute for Biophysical Chemistry (DE)
- Corresponding author
- Gagneur, Julien
- Venue
- RNA
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2017-08-11
- Volume
- 23
- Issue
- 11
- Pages
- 1648-1659
- ISSN
- 1355-8382 (ISSN-L)
- 1469-9001
- PMC
- PMC5648033
- OpenAlex
- W2610908544
- Cited by
- 79
- References
- 7
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 10 · 2023: 3 · 2022: 8 · 2021: 17 · 2020: 9 · 2019: 10 · 2018: 10
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- RNA (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Fabien Bonneau
- Deutsche Forschungsgemeinschaft
- QBM
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- mRNA stability, mRNA half-life, cis-regulatory elements, codon usage, single nucleotide variants, upstream AUGs, Xrn1, nonsense-mediated mRNA decay, no-go decay, decapping, deadenylation, gene expression regulation, Saccharomyces cerevisiae
- MeSH terms
- Base Sequence, Codon, Genes, Fungal, Half-Life, Models, Biological, Peptide Chain Initiation, Translational, RNA, Fungal, RNA, Messenger, Saccharomyces cerevisiae, Schizosaccharomyces, 3' Untranslated Regions, RNA Stability, Regulatory Elements, Transcriptional, Gene Knockout Techniques, Nonsense Mediated mRNA Decay
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