The landscape of molecular chaperones across human tissues reveals a layered architecture of core and variable chaperones [article]

Netta Shemesh, Juman Jubran, Mehtap Abu-Qarn, Eyal Simonovky, Omer Basha, Idan Hekselman, Shiran Dror, Ekaterina Vinogradov, Serena Carra, Anat Ben-Zvi, Esti Yeger-Lotem
2020 bioRxiv   pre-print
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. Here, we used human tissue RNA-sequencing profiles to analyze the expression and organization of chaperones across 29 main tissues. We found that relative to protein-coding genes, chaperones were significantly more ubiquitously and highly expressed across all tissues.
more » ... differential expression analysis revealed that most chaperones were up- or down-regulated in certain tissues, suggesting that they have tissue-specific roles. In agreement, chaperones that were upregulated in skeletal muscle were highly enriched in mouse myoblasts and in nematode's muscle tissue, and overlapped significantly with chaperones that are causal for muscle diseases. We also identified a distinct subset of chaperones that formed a uniformly-expressed, cross-family core group conducting basic cellular functions that was significantly more essential for cell survival. Altogether, this suggests a layered architecture of chaperones across tissues that is composed of shared core elements that are complemented by variable elements which give rise to tissue-specific functions and sensitivities, thereby contributing to the tissue-specificity of protein misfolding diseases.
doi:10.1101/2020.03.04.976720 fatcat:kf5prvmklzcbrig4x74s2je34u