Cis-regulatory elements explain most of the mRNA stability variation across genes in yeast
Cheng J, Maier KC, Avsec Z, Rus P, Gagneur J (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 23
Pages Range: 1648-1659
Journal Issue: 11
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.
Involved external institutions
Technische Universität München (TUM)
Germany (DE)
Max-Planck-Institut für biophysikalische Chemie (Karl-Friedrich-Bonhoeffer-Institut) / Max Planck Institute for Biophysical Chemistry
Germany (DE)
Germany (DE)
Max-Planck-Institut für biophysikalische Chemie (Karl-Friedrich-Bonhoeffer-Institut) / Max Planck Institute for Biophysical Chemistry
Germany (DE)
How to cite
APA:
Cheng, J., Maier, K.C., Avsec, Z., Rus, P., & Gagneur, J. (2017). Cis-regulatory elements explain most of the mRNA stability variation across genes in yeast. Rna-A Publication of the Rna Society, 23(11), 1648-1659. https://doi.org/10.1261/rna.062224.117
MLA:
Cheng, Jun, et al. "Cis-regulatory elements explain most of the mRNA stability variation across genes in yeast." Rna-A Publication of the Rna Society 23.11 (2017): 1648-1659.
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