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Cis-regulatory elements explain most of the mRNA stability variation across genes in yeast
Open accessPreprint — published as 10.1261/rna.062224.117 · Paper page
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 60% 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 non-sense 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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Global quantification of mammalian gene expression control
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Codon Optimality Is a Major Determinant of mRNA Stability
Presnyak, V., Alhusaini, N., Chen, Y.-H., Martin, S., Morris, N., Kline, N., Olson, S., Weinberg, D., Baker, K. E., Graveley, B. R., et al. (2015) · Cell · doi:10.1016/j.cell.2015.02.029 · Cited by 1,078 · cited 2×
“For those synonymous variations that changed half-life by more than 2%, most of them were variations that involved the most non-optimized codons CGA or ATA (Supplementary Figure 8, Presnyak et al. 2015).”
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Metadata
- 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
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2016-11-03
- OpenAlex
- W2547963061
- Cited by
- 1
- References
- 5
- Citations by year
- 2018: 1
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- 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, Saccharomyces cerevisiae, no-go decay, deadenylation, decapping, gene expression regulation
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