The landscape of molecular chaperones across human tissues reveals a layered architecture of core and variable chaperones.
The landscape of molecular chaperones across human tissues reveals a layered architecture of core and variable chaperones.
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DOI：
10.1038/s41467-021-22369-9
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发表时间：
2021-04-12
影响因子：
16.6
通讯作者：
Yeger-Lotem E
中科院分区：
文献类型：
--
作者：
Shemesh N;Jubran J;Dror S;Simonovsky E;Basha O;Argov C;Hekselman I;Abu-Qarn M;Vinogradov E;Mauer O;Tiago T;Carra S;Ben-Zvi A;Yeger-Lotem E
蛋白质折叠环境对分子伴侣破坏的敏感性可以是高度组织特异性的。然而，组织的分子伴侣系统跨生理人体组织很少受到关注。通过对大规模组织转录组的计算分析，我们揭示了分子伴侣系统是由跨组织均匀表达的核心元件和差异表达以适应组织特异性要求的可变元件组成的。我们通过蛋白质组学分析表明，肌肉特异性签名是功能性的和保守的。核心分子伴侣在整个组织中显著更丰富，并且比可变分子伴侣对细胞存活更重要。与可变的分子伴侣一起，它们形成组织特异性功能网络。对人类器官发育和衰老大脑转录组的分析表明，这些功能网络是在发育中建立的，并随着年龄的增长而下降。在这项工作中，我们扩展了已知的从头与应力诱导真核分子伴侣的功能组织成一个分层的核心可变架构在多细胞生物。蛋白质折叠能力的组织特异性差异知之甚少。在这里，作者表明，人类分子伴侣系统由无处不在的核心分子伴侣和组织特异性可变分子伴侣组成，其扰动导致组织特异性表型。
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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影响因子：
4.3
作者：
Barshir R;Shwartz O;Smoly IY;Yeger-Lotem E
通讯作者：
Yeger-Lotem E
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
8.8
作者：
Brehme M;Voisine C;Rolland T;Wachi S;Soper JH;Zhu Y;Orton K;Villella A;Garza D;Vidal M;Ge H;Morimoto RI
通讯作者：
Morimoto RI
影响因子：
64.5
作者：
Albanèse, V;Yam, AYW;Frydman, J
通讯作者：
Frydman, J
影响因子：
7.2
作者：
Biebl, Maximilian M.;Buchner, Johannes
通讯作者：
Buchner, Johannes