Adaptive preservation of orphan ribosomal proteins in chaperone-dispersed condensates.
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
05
12
2022
accepted:
12
09
2023
medline:
13
11
2023
pubmed:
17
10
2023
entrez:
16
10
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37845327
doi: 10.1038/s41556-023-01253-2
pii: 10.1038/s41556-023-01253-2
doi:
Substances chimiques
Ribosomal Proteins
0
Saccharomyces cerevisiae Proteins
0
HSP40 Heat-Shock Proteins
0
HSP70 Heat-Shock Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1691-1703Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : GM138689
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : GM144278
Organisme : National Science Foundation (NSF)
ID : OMA-2121044
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Warner, J. R. The economics of ribosome biosynthesis in yeast. Trends Biochem. Sci. 24, 437–440 (1999).
pubmed: 10542411
Maaløe, O. & Kjeldgaard, N. O. Control of macromolecular synthesis; a study of DNA, RNA, and protein synthesis in bacteria. (W. A. Benjamin, 1966).
Scott, M., Klumpp, S., Mateescu, E. M. & Hwa, T. Emergence of robust growth laws from optimal regulation of ribosome synthesis. Mol. Syst. Biol. 10, 747 (2014).
pubmed: 25149558
pmcid: 4299513
Lempiainen, H. & Shore, D. Growth control and ribosome biogenesis. Curr. Opin. Cell Biol. 21, 855–863 (2009).
pubmed: 19796927
Ingolia, N. T., Ghaemmaghami, S., Newman, J. R. & Weissman, J. S. Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science 324, 218–223 (2009).
pubmed: 19213877
pmcid: 2746483
Shore, D. & Albert, B. Ribosome biogenesis and the cellular energy economy. Curr. Biol. 32, R611–R617 (2022).
pubmed: 35728540
Woolford, J. L. Jr. & Baserga, S. J. Ribosome biogenesis in the yeast Saccharomyces cerevisiae. Genetics 195, 643–681 (2013).
pubmed: 24190922
pmcid: 3813855
Jakel, S., Mingot, J. M., Schwarzmaier, P., Hartmann, E. & Gorlich, D. Importins fulfil a dual function as nuclear import receptors and cytoplasmic chaperones for exposed basic domains. EMBO J. 21, 377–386 (2002).
pubmed: 11823430
pmcid: 125346
Pillet, B., Mitterer, V., Kressler, D. & Pertschy, B. Hold on to your friends: dedicated chaperones of ribosomal proteins: dedicated chaperones mediate the safe transfer of ribosomal proteins to their site of pre-ribosome incorporation. Bioessays 39, 1–12 (2017).
pubmed: 27859409
Gasch, A. P. & Werner-Washburne, M. The genomics of yeast responses to environmental stress and starvation. Funct. Integr. Genomics 2, 181–192 (2002).
pubmed: 12192591
Gasch, A. P. et al. Genomic expression programs in the response of yeast cells to environmental changes. Mol. Biol. Cell 11, 4241–4257 (2000).
pubmed: 11102521
pmcid: 15070
Sawarkar, R. Transcriptional lockdown during acute proteotoxic stress. Trends Biochem. Sci. 47, 660–672 (2022).
pubmed: 35487807
pmcid: 9041648
Shore, D., Zencir, S. & Albert, B. Transcriptional control of ribosome biogenesis in yeast: links to growth and stress signals. Biochem. Soc. Trans. 49, 1589–1599 (2021).
pubmed: 34240738
pmcid: 8421047
Iserman, C. et al. Condensation of Ded1p promotes a translational switch from housekeeping to stress protein production. Cell 181, 818–831 e819 (2020).
pubmed: 32359423
pmcid: 7237889
Muhlhofer, M. et al. The heat shock response in yeast maintains protein homeostasis by chaperoning and replenishing proteins. Cell Rep. 29, 4593–4607 e4598 (2019).
pubmed: 31875563
Juszkiewicz, S. & Hegde, R. S. Quality control of orphaned proteins. Mol. Cell 71, 443–457 (2018).
pubmed: 30075143
pmcid: 6624128
Yanagitani, K., Juszkiewicz, S. & Hegde, R. S. UBE2O is a quality control factor for orphans of multiprotein complexes. Science 357, 472–475 (2017).
pubmed: 28774922
pmcid: 5549844
Sung, M. K. et al. A conserved quality-control pathway that mediates degradation of unassembled ribosomal proteins. eLife 5, e19105 (2016).
pubmed: 27552055
pmcid: 5026473
Narla, A. & Ebert, B. L. Ribosomopathies: human disorders of ribosome dysfunction. Blood 115, 3196–3205 (2010).
pubmed: 20194897
pmcid: 2858486
Pincus, D. Regulation of Hsf1 and the heat shock response. Adv. Exp. Med Biol. 1243, 41–50 (2020).
pubmed: 32297210
Albert, B. et al. A ribosome assembly stress response regulates transcription to maintain proteome homeostasis. eLife 8, e45002 (2019).
pubmed: 31124783
pmcid: 6579557
Tye, B. W. et al. Proteotoxicity from aberrant ribosome biogenesis compromises cell fitness. eLife 8, e43002 (2019).
pubmed: 30843788
pmcid: 6453566
Feder, Z. A. et al. Subcellular localization of the J-protein Sis1 regulates the heat shock response. J. Cell Biol. 220, e202005165 (2021).
pubmed: 33326013
Garde, R., Singh, A., Ali, A. & Pincus, D. Transcriptional regulation of Sis1 promotes fitness but not feedback in the heat shock response. eLife 12, e79444 (2023).
pubmed: 37158601
pmcid: 10191621
Masser, A. E. et al. Cytoplasmic protein misfolding titrates Hsp70 to activate nuclear Hsf1. eLife 8, e47791 (2019).
pubmed: 31552827
pmcid: 6779467
Triandafillou, C. G., Katanski, C. D., Dinner, A. R. & Drummond, D. A. Transient intracellular acidification regulates the core transcriptional heat shock response. eLife 9, e54880 (2020).
pubmed: 32762843
pmcid: 7449696
Tye, B. W. & Churchman, L. S. Hsf1 activation by proteotoxic stress requires concurrent protein synthesis. Mol. Biol. Cell 32, 1800–1806 (2021).
pubmed: 34191586
pmcid: 8684711
Frottin, F. et al. The nucleolus functions as a phase-separated protein quality control compartment. Science 365, 342–347 (2019).
pubmed: 31296649
Gallardo, P., Real-Calderon, P., Flor-Parra, I., Salas-Pino, S. & Daga, R. R. Acute heat stress leads to reversible aggregation of nuclear proteins into nucleolar rings in fission yeast. Cell Rep. 33, 108377 (2020).
pubmed: 33176152
Hung, V. et al. Spatially resolved proteomic mapping in living cells with the engineered peroxidase APEX2. Nat. Protoc. 11, 456–475 (2016).
pubmed: 26866790
pmcid: 4863649
Sailer, C. et al. A comprehensive landscape of 60S ribosome biogenesis factors. Cell Rep. 38, 110353 (2022).
pubmed: 35139378
pmcid: 8884084
An, H., Ordureau, A., Korner, M., Paulo, J. A. & Harper, J. W. Systematic quantitative analysis of ribosome inventory during nutrient stress. Nature 583, 303–309 (2020).
pubmed: 32612236
pmcid: 7351614
Garshott, D. M. et al. iRQC, a surveillance pathway for 40S ribosomal quality control during mRNA translation initiation. Cell Rep. 36, 109642 (2021).
pubmed: 34469731
pmcid: 8997904
Klaips, C. L., Gropp, M. H. M., Hipp, M. S. & Hartl, F. U. Sis1 potentiates the stress response to protein aggregation and elevated temperature. Nat. Commun. 11, 6271 (2020).
pubmed: 33293525
pmcid: 7722728
Schawalder, S. B. et al. Growth-regulated recruitment of the essential yeast ribosomal protein gene activator Ifh1. Nature 432, 1058–1061 (2004).
pubmed: 15616569
Thoreen, C. C. et al. A unifying model for mTORC1-mediated regulation of mRNA translation. Nature 485, 109–113 (2012).
pubmed: 22552098
pmcid: 3347774
Chowdhary, S., Kainth, A. S., Paracha, S., Gross, D. S. & Pincus, D. Inducible transcriptional condensates drive 3D genome reorganization in the heat shock response. Mol. Cell 82, 4386–4399.e7 (2022).
pubmed: 36327976
Craig, E. A. & Marszalek, J. How do J-proteins get Hsp70 to do so many different things? Trends Biochem. Sci. 42, 355–368 (2017).
pubmed: 28314505
pmcid: 5409888
Duster, R., Kaltheuner, I. H., Schmitz, M. & Geyer, M. 1,6-Hexanediol, commonly used to dissolve liquid–liquid phase separated condensates, directly impairs kinase and phosphatase activities. J. Biol. Chem. 296, 100260 (2021).
pubmed: 33814344
pmcid: 7948595
Muzzopappa, F. et al. Detecting and quantifying liquid–liquid phase separation in living cells by model-free calibrated half-bleaching. Nat. Commun. 13, 7787 (2022).
pubmed: 36526633
pmcid: 9758202
Lakowicz, J.R. Principles of Fluorescence Spectroscopy 3rd Edn (Springer, 2006).
Linsenmeier, M. et al. Dynamic arrest and aging of biomolecular condensates are modulated by low-complexity domains, RNA and biochemical activity. Nat. Commun. 13, 3030 (2022).
pubmed: 35641495
pmcid: 9156751
Cherkasov, V. et al. Coordination of translational control and protein homeostasis during severe heat stress. Curr. Biol. 23, 2452–2462 (2013).
pubmed: 24291094
Grousl, T. et al. Heat shock-induced accumulation of translation elongation and termination factors precedes assembly of stress granules in S. cerevisiae. PLoS ONE 8, e57083 (2013).
pubmed: 23451152
pmcid: 3581570
Riback, J. A. et al. Stress-triggered phase separation is an adaptive, evolutionarily tuned response. Cell 168, 1028–1040 e1019 (2017).
pubmed: 28283059
pmcid: 5401687
Yoo, H., Bard, J. A. M., Pilipenko, E. V. & Drummond, D. A. Chaperones directly and efficiently disperse stress-triggered biomolecular condensates. Mol. Cell 82, 741–755 e711 (2022).
pubmed: 35148816
pmcid: 8857057
Cereghetti, G. et al. Reversible amyloids of pyruvate kinase couple cell metabolism and stress granule disassembly. Nat. Cell Biol. 23, 1085–1094 (2021).
pubmed: 34616026
pmcid: 7611853
Kainth, A. S., Chowdhary, S., Pincus, D. & Gross, D. S. Primordial super-enhancers: heat shock-induced chromatin organization in yeast. Trends Cell Biol. 31, 801–813 (2021).
pubmed: 34001402
pmcid: 8448919
Rawat, P. et al. Stress-induced nuclear condensation of NELF drives transcriptional downregulation. Mol. Cell 81, 1013–1026 e1011 (2021).
pubmed: 33548202
pmcid: 7939545
Wallace, E. W. et al. Reversible, specific, active aggregates of endogenous proteins assemble upon heat stress. Cell 162, 1286–1298 (2015).
pubmed: 26359986
pmcid: 4567705
Brehme, M. et al. A chaperome subnetwork safeguards proteostasis in aging and neurodegenerative disease. Cell Rep. 9, 1135–1150 (2014).
pubmed: 25437566
pmcid: 4255334
Alberti, S. & Dormann, D. Liquid–liquid phase separation in disease. Annu. Rev. Genet 53, 171–194 (2019).
pubmed: 31430179
Alberti, S. & Hyman, A. A. Biomolecular condensates at the nexus of cellular stress, protein aggregation disease and ageing. Nat. Rev. Mol. Cell Biol. 22, 196–213 (2021).
pubmed: 33510441
Zheng, X. et al. Dynamic control of Hsf1 during heat shock by a chaperone switch and phosphorylation. eLife 5, e18638 (2016).
pubmed: 27831465
pmcid: 5127643
Mahat, D. B. & Lis, J. T. Use of conditioned media is critical for studies of regulation in response to rapid heat shock. Cell Stress Chaperones 22, 155–162 (2017).
pubmed: 27812889
Chen, B. C. et al. Lattice light-sheet microscopy: imaging molecules to embryos at high spatiotemporal resolution. Science 346, 1257998 (2014).
pubmed: 25342811
pmcid: 4336192
Northan, B. Ops-experiments. GitHub https://github.com/imagej/ops-experiments (2022).
Royer, L. A. et al. ClearVolume: open-source live 3D visualization for light-sheet microscopy. Nat. Methods 12, 480–481 (2015).
pubmed: 26020498
Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012).
pubmed: 22743772
Aboulhouda, S., Di Santo, R., Therizols, G. & Weinberg, D. Accurate, streamlined analysis of mRNA translation by sucrose gradient fractionation. Bio Protoc. 7, e2573 (2017).
pubmed: 29170751
pmcid: 5697790
Roy, R., Hohng, S. & Ha, T. A practical guide to single-molecule FRET. Nat. Methods 5, 507–516 (2008).
pubmed: 18511918
pmcid: 3769523
Michalet, X. Mean square displacement analysis of single-particle trajectories with localization error: Brownian motion in an isotropic medium. Phys. Rev. E 82, 041914 (2010).
Enkler, L. et al. Arf1 coordinates fatty acid metabolism and mitochondrial homeostasis. Nat. Cell Biol. 25, 1157–1172 (2023).
pubmed: 37400497
pmcid: 10415182