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The nucleolus functions as a phase-separated protein quality control compartment.

Science. 2019 Jul 11. pii: eaaw9157. doi: 10.1126/science.aaw9157. [Epub ahead of print]

Authors/Editors: Frottin F, Schueder F, Tiwary S, Gupta R, Körner R, Schlichthaerle T, Cox J, Jungmann R, Hartl FU, Hipp MS.
Publication Date: 2019

07_frottin

Abstract

The nuclear proteome is rich in stress-sensitive proteins, suggesting that effective protein quality control mechanisms are in place to ensure conformational maintenance. Here we investigated the role of the nucleolus in this process. In mammalian tissue culture cells, under stress conditions misfolded proteins entered the granular component (GC) phase of the nucleolus. Transient associations with nucleolar proteins such as NPM1 conferred low mobility to misfolded proteins within the liquid-like GC phase, avoiding irreversible aggregation. Refolding and extraction of proteins from the nucleolus during recovery from stress was Hsp70 dependent. The capacity of the nucleolus to store misfolded proteins was limited and prolonged stress led to a transition of the nucleolar matrix from liquid-like to solid, with loss of reversibility and dysfunction in quality control. Thus we suggest that the nucleolus has chaperone-like properties and can promote nuclear protein maintenance under stress.

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