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  The impact of genomic variation on protein phosphorylation states and regulatory networks

Grossbach, J., Gillet, L., Clement-Ziza, M., Schmalohr, C. L., Schubert, O. T., Schütter, M., et al. (2022). The impact of genomic variation on protein phosphorylation states and regulatory networks. Mol Syst Biol, 18(5), e10712. doi:10.15252/msb.202110712.

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Grossbach, J., Author
Gillet, L., Author
Clement-Ziza, M., Author
Schmalohr, C. L., Author
Schubert, O. T., Author
Schütter, M.1, Author           
Mawer, J. S. P.2, Author           
Barnes, C. A., Author
Bludau, I., Author
Weith, M., Author
Tessarz, P.2, Author           
Graef, M.1, Author           
Aebersold, R., Author
Beyer, A., Author
Affiliations:
1Graef – Autophagy and Cellular Ageing, Max Planck Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_1942295              
2Tessarz – Chromatin and Ageing, Max Planck Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_1942296              

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Free keywords: *Genome *Genomics Phosphorylation Proteome/genetics Saccharomyces cerevisiae/genetics *qtl *budding yeast *multi-omics genetic effects *phosphorylation *systems genetics
 Abstract: Genomic variation impacts on cellular networks by affecting the abundance (e.g., protein levels) and the functional states (e.g., protein phosphorylation) of their components. Previous work has focused on the former, while in this context, the functional states of proteins have largely remained neglected. Here, we generated high-quality transcriptome, proteome, and phosphoproteome data for a panel of 112 genomically well-defined yeast strains. Genetic effects on transcripts were generally transmitted to the protein layer, but specific gene groups, such as ribosomal proteins, showed diverging effects on protein levels compared with RNA levels. Phosphorylation states proved crucial to unravel genetic effects on signaling networks. Correspondingly, genetic variants that cause phosphorylation changes were mostly different from those causing abundance changes in the respective proteins. Underscoring their relevance for cell physiology, phosphorylation traits were more strongly correlated with cell physiological traits such as chemical compound resistance or cell morphology, compared with transcript or protein abundance. This study demonstrates how molecular networks mediate the effects of genomic variants to cellular traits and highlights the particular importance of protein phosphorylation.

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 Dates: 2022-05-012022
 Publication Status: Issued
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 Identifiers: Other: 35574625
DOI: 10.15252/msb.202110712
ISSN: 1744-4292 (Electronic)1744-4292 (Linking)
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Title: Mol Syst Biol
Source Genre: Journal
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Pages: - Volume / Issue: 18 (5) Sequence Number: - Start / End Page: e10712 Identifier: -