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Eraslan, B.* ; Wang, D.* ; Gusic, M. ; Prokisch, H. ; Hallström, B.M.* ; Uhlén, M.* ; Asplund, A.* ; Pontén, F.* ; Wieland, T.* ; Hopf, T.* ; Hahne, H.* ; Kuster, B.* ; Gagneur, J.*

Quantification and discovery of sequence determinants of protein-per-mRNA amount in 29 human tissues.

Mol. Syst. Biol. 15:e8513 (2019)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Despite their importance in determining protein abundance, a comprehensive catalogue of sequence features controlling protein-to-mRNA (PTR) ratios and a quantification of their effects are still lacking. Here, we quantified PTR ratios for 11,575 proteins across 29 human tissues using matched transcriptomes and proteomes. We estimated by regression the contribution of known sequence determinants of protein synthesis and degradation in addition to 45 mRNA and 3 protein sequence motifs that we found by association testing. While PTR ratios span more than 2 orders of magnitude, our integrative model predicts PTR ratios at a median precision of 3.2-fold. A reporter assay provided functional support for two novel UTR motifs, and an immobilized mRNA affinity competition-binding assay identified motif-specific bound proteins for one motif. Moreover, our integrative model led to a new metric of codon optimality that captures the effects of codon frequency on protein synthesis and degradation. Altogether, this study shows that a large fraction of PTR ratio variation in human tissues can be predicted from sequence, and it identifies many new candidate post-transcriptional regulatory elements.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Codon Usage ; Mrna Sequence Motifs ; Proteomics ; Transcriptomics ; Translational Control; Synonymous Codon Usage; Open Reading Frames; Au-rich-element; Binding Proteins; Gene-expression; Degradation Signals; Coding-sequence; Evolutionary Conservation; Translational Termination; Half-life
Sprache englisch
Veröffentlichungsjahr 2019
HGF-Berichtsjahr 2019
ISSN (print) / ISBN 1744-4292
e-ISSN 1744-4292
Zeitschrift Molecular Systems Biology
Quellenangaben Band: 15, Heft: 2, Seiten: , Artikelnummer: e8513 Supplement: ,
Verlag EMBO Press
Verlagsort 111 River St, Hoboken 07030-5774, Nj Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500700-001
DOI 10.15252/msb.20188513
WOS ID WOS:000459628300004
Scopus ID 85061855104
PubMed ID 30777893
Erfassungsdatum 2019-03-19
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