Article ; Online: Cyclophilin A supports translation of intrinsically disordered proteins and affects haematopoietic stem cell ageing.
2024 Volume 26, Issue 4, Page(s) 593–603
Abstract: Loss of protein function is a driving force of ageing. We have identified peptidyl-prolyl isomerase A (PPIA or cyclophilin A) as a dominant chaperone in haematopoietic stem and progenitor cells. Depletion of PPIA accelerates stem cell ageing. We found ... ...
| Abstract | Loss of protein function is a driving force of ageing. We have identified peptidyl-prolyl isomerase A (PPIA or cyclophilin A) as a dominant chaperone in haematopoietic stem and progenitor cells. Depletion of PPIA accelerates stem cell ageing. We found that proteins with intrinsically disordered regions (IDRs) are frequent PPIA substrates. IDRs facilitate interactions with other proteins or nucleic acids and can trigger liquid-liquid phase separation. Over 20% of PPIA substrates are involved in the formation of supramolecular membrane-less organelles. PPIA affects regulators of stress granules (PABPC1), P-bodies (DDX6) and nucleoli (NPM1) to promote phase separation and increase cellular stress resistance. Haematopoietic stem cell ageing is associated with a post-transcriptional decrease in PPIA expression and reduced translation of IDR-rich proteins. Here we link the chaperone PPIA to the synthesis of intrinsically disordered proteins, which indicates that impaired protein interaction networks and macromolecular condensation may be potential determinants of haematopoietic stem cell ageing. |
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| MeSH term(s) | Intrinsically Disordered Proteins/chemistry ; Cyclophilin A/genetics ; Cyclophilin A/metabolism ; RNA-Binding Proteins ; Hematopoietic Stem Cells/metabolism | ||||||||||
| Chemical Substances | Intrinsically Disordered Proteins ; Cyclophilin A (EC 5.2.1.-) ; RNA-Binding Proteins | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2024-03-29 | ||||||||||
| Publishing country | England | ||||||||||
| Document type | Journal Article | ||||||||||
| ZDB-ID | 1474722-4 | ||||||||||
| ISSN | 1476-4679 ; 1465-7392 | ||||||||||
| ISSN (online) | 1476-4679 | ||||||||||
| ISSN | 1465-7392 | ||||||||||
| DOI | 10.1038/s41556-024-01387-x | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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