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.

An adaptive biomolecular condensation response is conserved across environmentally divergent species.

Cells must sense and respond to sudden maladaptive environmental changes-stresses-to survive and thrive. Across eukaryotes, stresses such as heat shock trigger conserved responses: growth arrest, a specific transcriptional response, and biomolecular condensation of protein and mRNA into structures known as stress granules under severe stress. The composition, formation mechanism, adaptive significance, and even evolutionary conservation of these condensed structures remain enigmatic. Here we provide an unprecedented view into stress-triggered condensation, its evolutionary conservation and tuning, and its integration into other well-studied aspects of the stress response. Using three morphologically near-identical budding yeast species adapted to different thermal environments and diverged by up to 100 million years, we show that proteome-scale biomolecular condensation is tuned to species-specific thermal niches, closely tracking corresponding growth and transcriptional responses. In each species, poly(A)-binding protein-a core marker of stress granules-condenses in isolation at species-specific temperatures, with conserved molecular features and conformational changes modulating condensation. From the ecological to the molecular scale, our results reveal previously unappreciated levels of evolutionary selection in the eukaryotic stress response, while establishing a rich, tractable system for further inquiry.