The landscape of molecular chaperones across human tissues reveals a layered architecture of core-variable chaperones

ABSTRACT: 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 unveiled 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 of a mouse myoblast cell line that the muscle-specific signature is functional and conserved. Core chaperones were significantly more abundant across tissues and more important for cell survival than variable chaperones. Together with variable chaperones, they formed tissue-specific functional networks. Analysis of human organ development and aging brain transcriptomes revealed that these functional networks were maintained in development and declined with age. Our findings expand the known functional organization of de novo versus stress-inducible eukaryotic chaperones into a layered core-variable architecture in multi-cellular organisms.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Keren Bendalak  

LAB HEAD: Anat Ben-Zvi

PROVIDER: PXD022678 | Pride | 2021-02-08

REPOSITORIES: Pride