Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-22369-9
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Funding
- Israel Ministry of Science and Technology [3-14337]
- Israel Science Foundation [317/19, 278/18]
- MIUR [E91I18001480001]
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The authors demonstrate that the human chaperone system consists of ubiquitous core chaperones and tissue-specific variable chaperones, and perturbation of which leads to tissue-specific phenotypes. The core chaperones are significantly more abundant across tissues and important for cell survival, forming tissue-specific functional networks. This functional organization is established in development and declines with age, highlighting the importance of understanding tissue-specific differences in protein folding capacities.
The sensitivity of the protein-folding environment to chaperone disruption can be highly tissue-specific. Yet, the organization of the chaperone system across physiological human tissues has received little attention. Through computational analyses of large-scale tissue transcriptomes, we unveil that the chaperone system is composed of core elements that are uniformly expressed across tissues, and variable elements that are differentially expressed to fit with tissue-specific requirements. We demonstrate via a proteomic analysis that the muscle-specific signature is functional and conserved. Core chaperones are significantly more abundant across tissues and more important for cell survival than variable chaperones. Together with variable chaperones, they form tissue-specific functional networks. Analysis of human organ development and aging brain transcriptomes reveals that these functional networks are established in development and decline with age. In this work, we expand the known functional organization of de novo versus stress-inducible eukaryotic chaperones into a layered core-variable architecture in multi-cellular organisms. Tissue-specific differences in protein folding capacities are poorly understood. Here, the authors show that the human chaperone system consists of ubiquitous core chaperones and tissue-specific variable chaperones, perturbation of which leads to tissue-specific phenotypes.
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