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  Cis-regulatory elements explain most of the mRNA stability variation across genes in yeast.

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, 23(11), 1648-1659. doi:10.1261/rna.062224.117.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-18FC-3 Version Permalink: http://hdl.handle.net/21.11116/0000-0001-1C91-C
Genre: Journal Article

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 Creators:
Cheng, J., Author
Maier, K. C.1, Author              
Avsec, Z., Author
Rus, P.1, Author              
Gagneur, J., Author
Affiliations:
1Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1863498              

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Free keywords: cis-regulatory elements; codon optimality; mRNA half-life
 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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Language(s): eng - English
 Dates: 2017-08-112017-11
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1261/rna.062224.117
 Degree: -

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Title: RNA
Source Genre: Journal
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Pages: - Volume / Issue: 23 (11) Sequence Number: - Start / End Page: 1648 - 1659 Identifier: -