Natural proteome diversity links aneuploidy tolerance to protein turnover.

Autor: Muenzner J; Department of Biochemistry, Charité Universitätsmedizin, Berlin, Germany., Trébulle P; Molecular Biology of Metabolism Laboratory, Francis Crick Institute, London, UK.; Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK., Agostini F; Department of Biochemistry, Charité Universitätsmedizin, Berlin, Germany., Zauber H; Max Delbrück Center for Molecular Medicine, Berlin, Germany., Messner CB; Molecular Biology of Metabolism Laboratory, Francis Crick Institute, London, UK.; Precision Proteomics Center, Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland., Steger M; Evotec (München), Martinsried, Germany.; NEOsphere Biotechnologies, Martinsried, Germany., Kilian C; Department of Biochemistry, Charité Universitätsmedizin, Berlin, Germany., Lau K; Department of Biochemistry, Charité Universitätsmedizin, Berlin, Germany., Barthel N; Department of Biochemistry, Charité Universitätsmedizin, Berlin, Germany., Lehmann A; Department of Biochemistry, Charité Universitätsmedizin, Berlin, Germany., Textoris-Taube K; Department of Biochemistry, Charité Universitätsmedizin, Berlin, Germany.; Core Facility High-Throughput Mass Spectrometry, Charité Universitätsmedizin, Berlin, Germany., Caudal E; Université de Strasbourg, CNRS GMGM UMR 7156, Strasbourg, France., Egger AS; Molecular Biology of Metabolism Laboratory, Francis Crick Institute, London, UK., Amari F; Department of Biochemistry, Charité Universitätsmedizin, Berlin, Germany.; Core Facility High-Throughput Mass Spectrometry, Charité Universitätsmedizin, Berlin, Germany., De Chiara M; Université Côte d'Azur, CNRS, INSERM, IRCAN, Nice, France., Demichev V; Department of Biochemistry, Charité Universitätsmedizin, Berlin, Germany.; Molecular Biology of Metabolism Laboratory, Francis Crick Institute, London, UK., Gossmann TI; Computational Systems Biology, Faculty of Biochemical and Chemical Engineering, TU Dortmund University, Dortmund, Germany., Mülleder M; Core Facility High-Throughput Mass Spectrometry, Charité Universitätsmedizin, Berlin, Germany., Liti G; Université Côte d'Azur, CNRS, INSERM, IRCAN, Nice, France., Schacherer J; Université de Strasbourg, CNRS GMGM UMR 7156, Strasbourg, France.; Institut Universitaire de France (IUF), Paris, France., Selbach M; Max Delbrück Center for Molecular Medicine, Berlin, Germany., Berman J; Shmunis School of Biomedical and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel. jberman@tauex.tau.ac.il., Ralser M; Department of Biochemistry, Charité Universitätsmedizin, Berlin, Germany. markus.ralser@charite.de.; Molecular Biology of Metabolism Laboratory, Francis Crick Institute, London, UK. markus.ralser@charite.de.; Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK. markus.ralser@charite.de.; Max Planck Institute for Molecular Genetics, Berlin, Germany. markus.ralser@charite.de.
Jazyk: angličtina
Zdroj: Nature [Nature] 2024 Jun; Vol. 630 (8015), pp. 149-157. Date of Electronic Publication: 2024 May 22.
DOI: 10.1038/s41586-024-07442-9
Abstrakt: Accessing the natural genetic diversity of species unveils hidden genetic traits, clarifies gene functions and allows the generalizability of laboratory findings to be assessed. One notable discovery made in natural isolates of Saccharomyces cerevisiae is that aneuploidy-an imbalance in chromosome copy numbers-is frequent 1,2 (around 20%), which seems to contradict the substantial fitness costs and transient nature of aneuploidy when it is engineered in the laboratory 3-5 . Here we generate a proteomic resource and merge it with genomic 1 and transcriptomic 6 data for 796 euploid and aneuploid natural isolates. We find that natural and lab-generated aneuploids differ specifically at the proteome. In lab-generated aneuploids, some proteins-especially subunits of protein complexes-show reduced expression, but the overall protein levels correspond to the aneuploid gene dosage. By contrast, in natural isolates, more than 70% of proteins encoded on aneuploid chromosomes are dosage compensated, and average protein levels are shifted towards the euploid state chromosome-wide. At the molecular level, we detect an induction of structural components of the proteasome, increased levels of ubiquitination, and reveal an interdependency of protein turnover rates and attenuation. Our study thus highlights the role of protein turnover in mediating aneuploidy tolerance, and shows the utility of exploiting the natural diversity of species to attain generalizable molecular insights into complex biological processes.
(© 2024. The Author(s).)
Databáze: MEDLINE
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