Adaptive preservation of orphan ribosomal proteins in chaperone-dispersed condensates

Ribosome biogenesis is among the most resource-intensive cellular processes, with ribosomal proteins accounting for up to half of all newly synthesized proteins in eukaryotic cells. During stress, cells shut down ribosome biogenesis in part by halting rRNA synthesis, potentially leading to massive accumulation of aggregation-prone 'orphan' ribosomal proteins (oRPs). Here we show that, during heat shock in yeast and human cells, oRPs accumulate as reversible peri-nucleolar condensates recognized by the Hsp70 co-chaperone Sis1/DnaJB6. oRP condensates are liquid-like in cell-free lysate but solidify upon depletion of Sis1 or inhibition of Hsp70. When cells recover from heat shock, oRP condensates disperse in a Sis1- and Hsp70-dependent manner, and the oRP constituents are incorporated into functional ribosomes in the cytosol, enabling cells to efficiently resume growth. Preserving biomolecules in reversible condensates-like mRNAs in cytosolic stress granules and oRPs at the nucleolar periphery-may be a primary function of the Hsp70 chaperone system. Ali et al. show that, during heat shock, aggregation-prone orphan ribosomal proteins form nucleolar-associated condensates that are kept in a liquid-like and reusable state through Hsp70 and its co-chaperones.

Automated summary

During stress, cells halt ribosome biogenesis, leading to accumulation of aggregation-prone orphan ribosomal proteins (oRPs). A study shows that these oRPs form reversible peri-nucleolar condensates recognized by Hsp70 co-chaperone Sis1/DnaJB6 during heat shock. These condensates remain in a liquid-like state through Hsp70 and its co-chaperones. Upon recovery, these condensates disperse in a Sis1- and Hsp70-dependent manner, with the oRPs being incorporated back into functional ribosomes in the cytosol.