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- Eraslan, Basak, et al.
(författare)
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Quantification and discovery of sequence determinants of protein-per-mRNA amount in 29 human tissues
- 2019
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Ingår i: Molecular Systems Biology. - : WILEY. - 1744-4292 .- 1744-4292. ; 15:2
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Wang, Dongxue, et al.
(författare)
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A deep proteome and transcriptome abundance atlas of 29 healthy human tissues
- 2019
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Ingår i: Molecular Systems Biology. - : WILEY. - 1744-4292 .- 1744-4292. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- Genome-, transcriptome- and proteome-wide measurements provide insights into how biological systems are regulated. However, fundamental aspects relating to which human proteins exist, where they are expressed and in which quantities are not fully understood. Therefore, we generated a quantitative proteome and transcriptome abundance atlas of 29 paired healthy human tissues from the Human Protein Atlas project representing human genes by 18,072 transcripts and 13,640 proteins including 37 without prior protein-level evidence. The analysis revealed that hundreds of proteins, particularly in testis, could not be detected even for highly expressed mRNAs, that few proteins show tissue-specific expression, that strong differences between mRNA and protein quantities within and across tissues exist and that protein expression is often more stable across tissues than that of transcripts. Only 238 of 9,848 amino acid variants found by exome sequencing could be confidently detected at the protein level showing that proteogenomics remains challenging, needs better computational methods and requires rigorous validation. Many uses of this resource can be envisaged including the study of gene/protein expression regulation and biomarker specificity evaluation.
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