Format

Send to

Choose Destination
Mol Syst Biol. 2019 Feb 18;15(2):e8513. doi: 10.15252/msb.20188513.

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

Author information

1
Computational Biology, Department of Informatics, Technical University of Munich, Garching Munich, Germany.
2
Graduate School of Quantitative Biosciences (QBM), Ludwig-Maximilians-Universität München, Munich, Germany.
3
Chair of Proteomics and Bioanalytics, Technical University of Munich, Freising, Germany.
4
Institute of Human Genetics, Technical University of Munich, Munich, Germany.
5
Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
6
Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden.
7
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
8
OmicScouts GmbH, Freising, Germany hannes.hahne@omicscouts.com kuster@tum.de gagneur@in.tum.de.
9
Chair of Proteomics and Bioanalytics, Technical University of Munich, Freising, Germany hannes.hahne@omicscouts.com kuster@tum.de gagneur@in.tum.de.
10
Center For Integrated Protein Science Munich (CIPSM), Munich, Germany.
11
Computational Biology, Department of Informatics, Technical University of Munich, Garching Munich, Germany hannes.hahne@omicscouts.com kuster@tum.de gagneur@in.tum.de.

Abstract

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.

KEYWORDS:

codon usage; mRNA sequence motifs; proteomics; transcriptomics; translational control

PMID:
30777893
PMCID:
PMC6379048
DOI:
10.15252/msb.20188513
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center