Sequence signatures and mRNA concentration can explain two-thirds of protein abundance variation in a human cell line

By Christine Vogel, Raquel P. de Sousa Abreu, Daijin Ko, S. Le, B. Shapiro, S. Burns, D. Sandhu, D. Boutz, Edward M. Marcotte, L. Penalva. Molecular Systems Biology, 2010

651 citations recorded by the source corpus.

Transcription, mRNA decay, translation and protein degradation are essential processes during eukaryotic gene expression, but their relative global contributions to steady‐state protein concentrations in multi‐cellular eukaryotes are largely unknown. Using measurements of absolute protein and mRNA abundances in cellular lysate from the human Daoy medulloblastoma cell line, we quantitatively evaluate the impact of mRNA concentration and sequence features implicated in translation and protein degradation on protein expression. Sequence features related to translation and protein degradation have an impact similar to that of mRNA abundance, and their combined contribution explains two‐thirds of protein abundance variation. mRNA sequence lengths, amino‐acid properties, upstream open reading frames and secondary structures in the 5′ untranslated region (UTR) were the strongest individual correlates of protein concentrations. In a combined model, characteristics of the coding region and the 3′UTR explained a larger proportion of protein abundance variation than characteristics of the 5′UTR. The absolute protein and mRNA concentration measurements for >1000 human genes described here represent one of the largest datasets currently available, and reveal both general trends and specific examples of post‐transcriptional regulation.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/52473f71305c179dfe56998ae2df919d41650add

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Citations in the corpus

Enhancing the Prioritization of Disease-Causing Genes through Tissue Specific Protein Interaction Networks (2012, background): “Posttranscriptional modifications or higher translational efficiency may also result in higher protein levels or longer protein half-lives [46,47].”
Understanding the contribution of synonymous mutations to human disease (2011, background): “A comprehensive characterization of determinants of human protein abundanc”
Synonymous but not the same: the causes and consequences of codon bias (2010, background): “Measurements of endogenous expression Recent developments in mass spectrometry and fluorescence microscopy allow large-scale measurements of endogenous protein level”
A deep proteome and transcriptome abundance atlas of 29 healthy human tissues (2018, methodology): “Messenger RNA levels are important determinants for protein abundance (Vogel et al. 2010; Schwanhäusser et al. 2011) and extensive mRNA expression maps of human cell types and tissues have been generated as proxies for estimating protein abundance (GTEx Consortium 2013; Uhlén et al. 2015; Thul et…”
Toward a Kinetic Understanding of Eukaryotic Translation. (2018, background): “It has been estimated that codon optimality can account for about 30% of the variation that exists between mRNA abundance and protein abundance in human cells (Vogel et al. 2010; Hanson and Coller 2018).”
Polyploidy, the Nucleotype, and Novelty: The Impact of Genome Doubling on the Biology of the Cell (2019, background): “Protein stability (i.e., rate of protein degradation) is a significant regulator of steady-state protein abundance (Vogel et al. 2010; Vogel and Marcotte 2012).”