PT  - JOURNAL ARTICLE
AU  - Cheng, Jun
AU  - Maier, Kerstin C.
AU  - Avsec, Žiga
AU  - Rus, Petra
AU  - Gagneur, Julien
TI  - Cis-regulatory elements explain most of the mRNA stability variation across genes in yeast
AID  - 10.1101/085522
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 085522
4099  - http://biorxiv.org/content/early/2017/04/27/085522.short
4100  - http://biorxiv.org/content/early/2017/04/27/085522.full
AB  - 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.