Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL, USA.
Committee on Genetics, Genomics, and Systems Biology, University of Chicago, Chicago, IL, USA.
Nat Cell Biol. 2023 Nov;25(11):1691-1703. doi: 10.1038/s41556-023-01253-2. Epub 2023 Oct 16.
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.
核糖体生物发生是细胞中资源消耗最多的过程之一，核糖体蛋白占真核细胞中新合成蛋白质的一半以上。在应激条件下，细胞通过停止 rRNA 合成部分关闭核糖体生物发生，这可能导致易于聚集的“孤儿”核糖体蛋白（oRPs）大量积累。在这里，我们发现在酵母和人类细胞的热激过程中，oRPs 作为可逆的核仁周凝聚物积累，被 Hsp70 共伴侣 Sis1/DnaJB6 识别。oRP 凝聚物在无细胞溶酶体中呈液态，但在 Sis1 耗尽或 Hsp70 抑制时会凝固。当细胞从热激中恢复时，oRP 凝聚物以 Sis1 和 Hsp70 依赖的方式分散，oRP 成分被整合到细胞质中的功能性核糖体中，使细胞能够有效地恢复生长。将生物分子保存在可逆凝聚物中，如细胞质应激颗粒中的 mRNAs 和核仁周围的 oRPs，可能是 Hsp70 伴侣系统的主要功能之一。
