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Isoform-resolved correlation analysis between mRNA abundance regulation and protein level degradation
B. Salovska, H. Zhu, T. Gandhi, M. Frank, W. Li, G. Rosenberger, C. Wu, PL. Germain, H. Zhou, Z. Hodny, L. Reiter, Y. Liu
Language English Country Great Britain
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
32175694
DOI
10.15252/msb.20199170
Knihovny.cz E-resources
- MeSH
- Alternative Splicing MeSH
- HeLa Cells MeSH
- Mass Spectrometry MeSH
- RNA Isoforms genetics metabolism MeSH
- Isotope Labeling methods MeSH
- Humans MeSH
- RNA, Messenger genetics metabolism MeSH
- Protein Isoforms analysis metabolism MeSH
- Proteins analysis metabolism MeSH
- Proteolysis MeSH
- Proteomics methods MeSH
- Workflow MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Profiling of biological relationships between different molecular layers dissects regulatory mechanisms that ultimately determine cellular function. To thoroughly assess the role of protein post-translational turnover, we devised a strategy combining pulse stable isotope-labeled amino acids in cells (pSILAC), data-independent acquisition mass spectrometry (DIA-MS), and a novel data analysis framework that resolves protein degradation rate on the level of mRNA alternative splicing isoforms and isoform groups. We demonstrated our approach by the genome-wide correlation analysis between mRNA amounts and protein degradation across different strains of HeLa cells that harbor a high grade of gene dosage variation. The dataset revealed that specific biological processes, cellular organelles, spatial compartments of organelles, and individual protein isoforms of the same genes could have distinctive degradation rate. The protein degradation diversity thus dissects the corresponding buffering or concerting protein turnover control across cancer cell lines. The data further indicate that specific mRNA splicing events such as intron retention significantly impact the protein abundance levels. Our findings support the tight association between transcriptome variability and proteostasis and provide a methodological foundation for studying functional protein degradation.
Biognosys Zurich Schlieren Switzerland
Department of Pharmacology Yale University School of Medicine New Haven CT USA
Department of Systems Biology Columbia University New York NY USA
European Molecular Biology Laboratory Heidelberg Germany
Institute for Neuroscience D HEST ETH Zurich Zurich Switzerland
Statistical Bioinformatics Lab DMLS University of Zürich Zurich Switzerland
Yale Cancer Biology Institute Yale University West Haven CT USA
References provided by Crossref.org
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