Proteotoxicity from aberrant ribosome biogenesis compromises cell fitness

Tye, Blake W.; Commins, Nicoletta; Ryazanova, Lillia V.; Wühr, Martin; Springer, Michael; Pincus, David; Churchman, L. Stirling

doi:10.7554/eLife.43002

Proteotoxicity from aberrant ribosome biogenesis compromises cell fitness

Journal Article · Thu Mar 07 00:00:00 EST 2019 · eLife

DOI:https://doi.org/10.7554/eLife.43002· OSTI ID:1502812

Tye, Blake W. ^[1]; Commins, Nicoletta ^[2]; Ryazanova, Lillia V. ^[3]; ^[3]; Springer, Michael ^[2]; ^[4]; ^[2]

Harvard Medical School, Boston, MA (United States); Harvard Univ., Cambridge, MA (United States); CABBI
Harvard Medical School, Boston, MA (United States)
Princeton Univ., Princeton, NJ (United States)
Whitehead Inst. for Biomedical Research, Cambridge, MA (United States); Univ. of Chicago, Chicago, IL (United States)

To achieve maximal growth, cells must manage a massive economy of ribosomal proteins (r-proteins) and RNAs (rRNAs) to produce thousands of ribosomes every minute. Although ribosomes are essential in all cells, natural disruptions to ribosome biogenesis lead to heterogeneous phenotypes. Here, we model these perturbations in Saccharomyces cerevisiae and show that challenges to ribosome biogenesis result in acute loss of proteostasis. Imbalances in the synthesis of r-proteins and rRNAs lead to the rapid aggregation of newly synthesized orphan r-proteins and compromise essential cellular processes, which cells alleviate by activating proteostasis genes. Exogenously bolstering the proteostasis network increases cellular fitness in the face of challenges to ribosome assembly, demonstrating the direct contribution of orphan r-proteins to cellular phenotypes. With this being said, we propose that ribosome assembly is a key vulnerability of proteostasis maintenance in proliferating cells that may be compromised by diverse genetic, environmental, and xenobiotic perturbations that generate orphan r-proteins.

View Accepted Manuscript (DOE)

Research Organization:: Univ. of Illinois, Champaign, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)

Grant/Contract Number:: SC0018420

OSTI ID:: 1502812

Journal Information:: eLife, Journal Name: eLife Vol. 8; ISSN 2050-084X

Publisher:: eLife Sciences Publications, Ltd.Copyright Statement

Country of Publication:: United States

Language:: English

References (112)

Rapid and reliable protein extraction from yeast Kushnirov, Vitaly V. Yeast, Vol. 16, Issue 9 https://doi.org/10.1002/1097-0061(20000630)16:9<857::AID-YEA561>3.0.CO;2-B	journal	January 2000
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 Pillet, Benjamin; Mitterer, Valentin; Kressler, Dieter BioEssays, Vol. 39, Issue 1 https://doi.org/10.1002/bies.201600153	journal	November 2016
Hsp70 accelerates the recovery of nucleolar morphology after heat shock. Pelham, H. R. The EMBO Journal, Vol. 3, Issue 13 https://doi.org/10.1002/j.1460-2075.1984.tb02264.x	journal	December 1984
Heat shock disassembles the nucleolus and inhibits nuclear protein import and poly(A)+ RNA export. Liu, Y.; Liang, S.; Tartakoff, A. M. The EMBO Journal, Vol. 15, Issue 23 https://doi.org/10.1002/j.1460-2075.1996.tb01064.x	journal	December 1996
Cotranscriptional events in eukaryotic ribosome synthesis: Cotranscriptional ribosome synthesis Turowski, Tomasz W.; Tollervey, David Wiley Interdisciplinary Reviews: RNA, Vol. 6, Issue 1 https://doi.org/10.1002/wrna.1263	journal	August 2014
Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution Stefani, Massimo; Dobson, Christopher M. Journal of Molecular Medicine, Vol. 81, Issue 11 https://doi.org/10.1007/s00109-003-0464-5	journal	November 2003
A method for the quantitative recovery of protein in dilute solution in the presence of detergents and lipids Wessel, D.; Flügge, U. I. Analytical Biochemistry, Vol. 138, Issue 1 https://doi.org/10.1016/0003-2697(84)90782-6	journal	April 1984
Phosphorylation of initiation factor 2α by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast Dever, Thomas E.; Feng, Lan; Wek, Ronald C. Cell, Vol. 68, Issue 3 https://doi.org/10.1016/0092-8674(92)90193-G	journal	February 1992
Hsp104, Hsp70, and Hsp40 Glover, John R.; Lindquist, Susan Cell, Vol. 94, Issue 1 https://doi.org/10.1016/S0092-8674(00)81223-4	journal	July 1998
The economics of ribosome biosynthesis in yeast Warner, Jonathan R. Trends in Biochemical Sciences, Vol. 24, Issue 11 https://doi.org/10.1016/S0968-0004(99)01460-7	journal	November 1999
Growth control and ribosome biogenesis Lempiäinen, Harri; Shore, David Current Opinion in Cell Biology, Vol. 21, Issue 6 https://doi.org/10.1016/j.ceb.2009.09.002	journal	December 2009
Yeast Life Span Extension by Depletion of 60S Ribosomal Subunits Is Mediated by Gcn4 Steffen, Kristan K.; MacKay, Vivian L.; Kerr, Emily O. Cell, Vol. 133, Issue 2 https://doi.org/10.1016/j.cell.2008.02.037	journal	April 2008
Amyloid-like Aggregates Sequester Numerous Metastable Proteins with Essential Cellular Functions Olzscha, Heidi; Schermann, Sonya M.; Woerner, Andreas C. Cell, Vol. 144, Issue 1 https://doi.org/10.1016/j.cell.2010.11.050	journal	January 2011
A Ribosome-Bound Quality Control Complex Triggers Degradation of Nascent Peptides and Signals Translation Stress Brandman, Onn; Stewart-Ornstein, Jacob; Wong, Daisy Cell, Vol. 151, Issue 5 https://doi.org/10.1016/j.cell.2012.10.044	journal	November 2012
PolyQ Proteins Interfere with Nuclear Degradation of Cytosolic Proteins by Sequestering the Sis1p Chaperone Park, Sae-Hun; Kukushkin, Yury; Gupta, Rajat Cell, Vol. 154, Issue 1 https://doi.org/10.1016/j.cell.2013.06.003	journal	July 2013
Organelle-Based Aggregation and Retention of Damaged Proteins in Asymmetrically Dividing Cells Zhou, Chuankai; Slaughter, Brian D.; Unruh, Jay R. Cell, Vol. 159, Issue 3 https://doi.org/10.1016/j.cell.2014.09.026	journal	October 2014
Reversible, Specific, Active Aggregates of Endogenous Proteins Assemble upon Heat Stress Wallace, Edward W. J.; Kear-Scott, Jamie L.; Pilipenko, Evgeny V. Cell, Vol. 162, Issue 6 https://doi.org/10.1016/j.cell.2015.08.041	journal	September 2015
Kinetic Analysis of Protein Stability Reveals Age-Dependent Degradation McShane, Erik; Sin, Celine; Zauber, Henrik Cell, Vol. 167, Issue 3 https://doi.org/10.1016/j.cell.2016.09.015	journal	October 2016
Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis Khajuria, Rajiv K.; Munschauer, Mathias; Ulirsch, Jacob C. Cell, Vol. 173, Issue 1 https://doi.org/10.1016/j.cell.2018.02.036	journal	March 2018
Cellular Strategies for Regulating Functional and Nonfunctional Protein Aggregation Gsponer, Jörg; Babu, M. Madan Cell Reports, Vol. 2, Issue 5 https://doi.org/10.1016/j.celrep.2012.09.036	journal	November 2012
Analysis of Nucleolar Protein Dynamics Reveals the Nuclear Degradation of Ribosomal Proteins Lam, Yun Wah; Lamond, Angus I.; Mann, Matthias Current Biology, Vol. 17, Issue 9 https://doi.org/10.1016/j.cub.2007.03.064	journal	May 2007
The Nuclear Proteome of a Vertebrate Wühr, Martin; Güttler, Thomas; Peshkin, Leonid Current Biology, Vol. 25, Issue 20 https://doi.org/10.1016/j.cub.2015.08.047	journal	October 2015
Spatially Organized Aggregation of Misfolded Proteins as Cellular Stress Defense Strategy Miller, Stephanie B. M.; Mogk, Axel; Bukau, Bernd Journal of Molecular Biology, Vol. 427, Issue 7 https://doi.org/10.1016/j.jmb.2015.02.006	journal	April 2015
Sch9 Is a Major Target of TORC1 in Saccharomyces cerevisiae Urban, Jörg; Soulard, Alexandre; Huber, Alexandre Molecular Cell, Vol. 26, Issue 5 https://doi.org/10.1016/j.molcel.2007.04.020	journal	June 2007
The Anchor-Away Technique: Rapid, Conditional Establishment of Yeast Mutant Phenotypes Haruki, Hirohito; Nishikawa, Junichi; Laemmli, Ulrich K. Molecular Cell, Vol. 31, Issue 6 https://doi.org/10.1016/j.molcel.2008.07.020	journal	September 2008
The Nucleolus under Stress Boulon, Séverine; Westman, Belinda J.; Hutten, Saskia Molecular Cell, Vol. 40, Issue 2 https://doi.org/10.1016/j.molcel.2010.09.024	journal	October 2010
Cellular Noise Regulons Underlie Fluctuations in Saccharomyces cerevisiae Stewart-Ornstein, Jacob; Weissman, Jonathan S.; El-Samad, Hana Molecular Cell, Vol. 45, Issue 4 https://doi.org/10.1016/j.molcel.2011.11.035	journal	February 2012
Widespread Regulation of Translation by Elongation Pausing in Heat Shock Shalgi, Reut; Hurt, Jessica A.; Krykbaeva, Irina Molecular Cell, Vol. 49, Issue 3 https://doi.org/10.1016/j.molcel.2012.11.028	journal	February 2013
Defining the Essential Function of Yeast Hsf1 Reveals a Compact Transcriptional Program for Maintaining Eukaryotic Proteostasis Solís, Eric J.; Pandey, Jai P.; Zheng, Xu Molecular Cell, Vol. 63, Issue 1 https://doi.org/10.1016/j.molcel.2016.05.014	journal	July 2016
Defining the Essential Function of Yeast Hsf1 Reveals a Compact Transcriptional Program for Maintaining Eukaryotic Proteostasis Solís, Eric J.; Pandey, Jai P.; Zheng, Xu Molecular Cell, Vol. 69, Issue 3 https://doi.org/10.1016/j.molcel.2018.01.021	journal	February 2018
A Puzzle of Life: Crafting Ribosomal Subunits Kressler, Dieter; Hurt, Ed; Baßler, Jochen Trends in Biochemical Sciences, Vol. 42, Issue 8 https://doi.org/10.1016/j.tibs.2017.05.005	journal	August 2017
Accurate, Sensitive, and Precise Multiplexed Proteomics Using the Complement Reporter Ion Cluster Sonnett, Matthew; Yeung, Eyan; Wühr, Martin Analytical Chemistry, Vol. 90, Issue 8 https://doi.org/10.1021/acs.analchem.7b04713	journal	March 2018
The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia Draptchinskaia, Natalia; Gustavsson, Peter; Andersson, Björn Nature Genetics, Vol. 21, Issue 2 https://doi.org/10.1038/5951	journal	February 1999
Cross‐species chemogenomic profiling reveals evolutionarily conserved drug mode of action Kapitzky, Laura; Beltrao, Pedro; Berens, Theresa J. Molecular Systems Biology, Vol. 6, Issue 1 https://doi.org/10.1038/msb.2010.107	journal	January 2010
Misfolded proteins partition between two distinct quality control compartments Kaganovich, Daniel; Kopito, Ron; Frydman, Judith Nature, Vol. 454, Issue 7208 https://doi.org/10.1038/nature07195	journal	August 2008
The Get1/2 transmembrane complex is an endoplasmic-reticulum membrane protein insertase Wang, Fei; Chan, Charlene; Weir, Nicholas R. Nature, Vol. 512, Issue 7515 https://doi.org/10.1038/nature13471	journal	July 2014
HSP70 sequestration by free α-globin promotes ineffective erythropoiesis in β-thalassaemia Arlet, Jean-Benoît; Ribeil, Jean-Antoine; Guillem, Flavia Nature, Vol. 514, Issue 7521 https://doi.org/10.1038/nature13614	journal	August 2014
Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol Wrobel, Lidia; Topf, Ulrike; Bragoszewski, Piotr Nature, Vol. 524, Issue 7566 https://doi.org/10.1038/nature14951	journal	August 2015
Synchronized mitochondrial and cytosolic translation programs Couvillion, Mary T.; Soto, Iliana C.; Shipkovenska, Gergana Nature, Vol. 533, Issue 7604 https://doi.org/10.1038/nature18015	journal	May 2016
Cytosolic proteostasis through importing of misfolded proteins into mitochondria Ruan, Linhao; Zhou, Chuankai; Jin, Erli Nature, Vol. 543, Issue 7645 https://doi.org/10.1038/nature21695	journal	March 2017
Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress Tkach, Johnny M.; Yimit, Askar; Lee, Anna Y. Nature Cell Biology, Vol. 14, Issue 9 https://doi.org/10.1038/ncb2549	journal	July 2012
Rsp5/Nedd4 is the main ubiquitin ligase that targets cytosolic misfolded proteins following heat stress Fang, Nancy N.; Chan, Gerard T.; Zhu, Mang Nature Cell Biology, Vol. 16, Issue 12 https://doi.org/10.1038/ncb3054	journal	October 2014
A comprehensive strategy enabling high-resolution functional analysis of the yeast genome Breslow, David K.; Cameron, Dale M.; Collins, Sean R. Nature Methods, Vol. 5, Issue 8 https://doi.org/10.1038/nmeth.1234	journal	July 2008
An auxin-based degron system for the rapid depletion of proteins in nonplant cells Nishimura, Kohei; Fukagawa, Tatsuo; Takisawa, Haruhiko Nature Methods, Vol. 6, Issue 12 https://doi.org/10.1038/nmeth.1401	journal	November 2009
High-efficiency yeast transformation using the LiAc/SS carrier DNA/PEG method Gietz, R. Daniel; Schiestl, Robert H. Nature Protocols, Vol. 2, Issue 1 https://doi.org/10.1038/nprot.2007.13	journal	January 2007
One-hour proteome analysis in yeast Richards, Alicia L.; Hebert, Alexander S.; Ulbrich, Arne Nature Protocols, Vol. 10, Issue 5 https://doi.org/10.1038/nprot.2015.040	journal	April 2015
Ribosome biogenesis in cancer: new players and therapeutic avenues Pelletier, Joffrey; Thomas, George; Volarević, Siniša Nature Reviews Cancer, Vol. 18, Issue 1 https://doi.org/10.1038/nrc.2017.104	journal	December 2017
Heat shock factors: integrators of cell stress, development and lifespan Åkerfelt, Malin; Morimoto, Richard I.; Sistonen, Lea Nature Reviews Molecular Cell Biology, Vol. 11, Issue 8 https://doi.org/10.1038/nrm2938	journal	July 2010
A multimeric assembly factor controls the formation of alternative 20S proteasomes Kusmierczyk, Andrew R.; Kunjappu, Mary J.; Funakoshi, Minoru Nature Structural & Molecular Biology, Vol. 15, Issue 3 https://doi.org/10.1038/nsmb.1389	journal	February 2008
Dactinomycin induces complete remission associated with nucleolar stress response in relapsed/refractory NPM1-mutated AML Gionfriddo, Ilaria; Brunetti, Lorenzo; Mezzasoma, Federica Leukemia https://doi.org/10.1038/s41375-021-01192-7	journal	March 2021
Adapting to stress — chaperome networks in cancer Joshi, Suhasini; Wang, Tai; Araujo, Thaís L. S. Nature Reviews Cancer, Vol. 18, Issue 9 https://doi.org/10.1038/s41568-018-0020-9	journal	May 2018
Ribosome biogenesis and cell growth: mTOR coordinates transcription by all three classes of nuclear RNA polymerases Mayer, C.; Grummt, I. Oncogene, Vol. 25, Issue 48 https://doi.org/10.1038/sj.onc.1209883	journal	October 2006
Complementary whole-genome technologies reveal the cellular response to proteasome inhibition by PS-341 Fleming, J. A.; Lightcap, E. S.; Sadis, S. Proceedings of the National Academy of Sciences, Vol. 99, Issue 3 https://doi.org/10.1073/pnas.032516399	journal	February 2002
Sfp1 is a stress- and nutrient-sensitive regulator of ribosomal protein gene expression Marion, R. M.; Regev, A.; Segal, E. Proceedings of the National Academy of Sciences, Vol. 101, Issue 40 https://doi.org/10.1073/pnas.0405353101	journal	September 2004
Misfolded proteins impose a dosage-dependent fitness cost and trigger a cytosolic unfolded protein response in yeast Geiler-Samerotte, K. A.; Dion, M. F.; Budnik, B. A. Proceedings of the National Academy of Sciences, Vol. 108, Issue 2 https://doi.org/10.1073/pnas.1017570108	journal	December 2010
Delayed Ras/PKA signaling augments the unfolded protein response Pincus, D.; Aranda-Diaz, A.; Zuleta, I. A. Proceedings of the National Academy of Sciences, Vol. 111, Issue 41 https://doi.org/10.1073/pnas.1409588111	journal	October 2014
Diazaborine Resistance in the Yeast Saccharomyces cerevisiae Reveals a Link between YAP1 and the Pleiotropic Drug Resistance Genes PDR1 and PDR3 Wendler, Franz; Bergler, Helmut; Prutej, Katja Journal of Biological Chemistry, Vol. 272, Issue 43 https://doi.org/10.1074/jbc.272.43.27091	journal	October 1997
Chemotherapeutic Drugs Inhibit Ribosome Biogenesis at Various Levels Burger, Kaspar; Mühl, Bastian; Harasim, Thomas Journal of Biological Chemistry, Vol. 285, Issue 16 https://doi.org/10.1074/jbc.M109.074211	journal	February 2010
The Drug Diazaborine Blocks Ribosome Biogenesis by Inhibiting the AAA-ATPase Drg1 Loibl, Mathias; Klein, Isabella; Prattes, Michael Journal of Biological Chemistry, Vol. 289, Issue 7 https://doi.org/10.1074/jbc.M113.536110	journal	December 2013
Misfolded Proteins Are Competent to Mediate a Subset of the Responses to Heat Shock in Saccharomyces cerevisiae Trotter, Eleanor W.; Kao, Camilla M. -F.; Berenfeld, Ludmilla Journal of Biological Chemistry, Vol. 277, Issue 47 https://doi.org/10.1074/jbc.M204686200	journal	September 2002
Amino Acid Substitutions in the C-terminal AAA ⁺ Module of Hsp104 Prevent Substrate Recognition by Disrupting Oligomerization and Cause High Temperature Inactivation Tkach, Johnny M.; Glover, John R. Journal of Biological Chemistry, Vol. 279, Issue 34 https://doi.org/10.1074/jbc.M400782200	journal	June 2004
Global Translational Responses to Oxidative Stress Impact upon Multiple Levels of Protein Synthesis Shenton, Daniel; Smirnova, Julia B.; Selley, Julian N. Journal of Biological Chemistry, Vol. 281, Issue 39 https://doi.org/10.1074/jbc.M601545200	journal	July 2006
A dual function for chaperones SSB–RAC and the NAC nascent polypeptide–associated complex on ribosomes Koplin, Ansgar; Preissler, Steffen; Ilina, Yulia The Journal of Cell Biology, Vol. 189, Issue 1 https://doi.org/10.1083/jcb.200910074	journal	April 2010
Genomic Expression Programs in the Response of Yeast Cells to Environmental Changes Gasch, Audrey P.; Spellman, Paul T.; Kao, Camilla M. Molecular Biology of the Cell, Vol. 11, Issue 12 https://doi.org/10.1091/mbc.11.12.4241	journal	December 2000
Genetic and epigenetic determinants establish a continuum of Hsf1 occupancy and activity across the yeast genome Pincus, David; Anandhakumar, Jayamani; Thiru, Prathapan Molecular Biology of the Cell, Vol. 29, Issue 26 https://doi.org/10.1091/mbc.E18-06-0353	journal	December 2018
Molecular chaperones and stress-inducible protein-sorting factors coordinate the spatiotemporal distribution of protein aggregates Malinovska, Liliana; Kroschwald, Sonja; Munder, Matthias C. Molecular Biology of the Cell, Vol. 23, Issue 16 https://doi.org/10.1091/mbc.e12-03-0194	journal	August 2012
Ribosomal proteins produced in excess are degraded by the ubiquitin–proteasome system Sung, Min-Kyung; Reitsma, Justin M.; Sweredoski, Michael J. Molecular Biology of the Cell, Vol. 27, Issue 17 https://doi.org/10.1091/mbc.e16-05-0290	journal	September 2016
Importins fulfil a dual function as nuclear import receptors and cytoplasmic chaperones for exposed basic domains Jäkel, Stefan; Mingot, José-Manuel; Schwarzmaier, Petra The EMBO Journal, Vol. 21, Issue 3 https://doi.org/10.1093/emboj/21.3.377	journal	February 2002
Role of eIF2α Kinases in Translational Control and Adaptation to Cellular Stress Wek, Ronald C. Cold Spring Harbor Perspectives in Biology, Vol. 10, Issue 7 https://doi.org/10.1101/cshperspect.a032870	journal	February 2018
Translational control by TOR and TAP42 through dephosphorylation of eIF2alpha kinase GCN2 Cherkasova, V. A. Genes & Development, Vol. 17, Issue 7 https://doi.org/10.1101/gad.1069003	journal	March 2003
Molecularchaperones as HSF1-specific transcriptional repressors Shi, Y.; Mosser, D. D.; Morimoto, R. I. Genes & Development, Vol. 12, Issue 5 https://doi.org/10.1101/gad.12.5.654	journal	March 1998
A dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell size Jorgensen, P. Genes & Development, Vol. 18, Issue 20 https://doi.org/10.1101/gad.1228804	journal	October 2004
Efficient termination of transcription by RNA polymerase I requires the 5' exonuclease Rat1 in yeast El Hage, A.; Koper, M.; Kufel, J. Genes & Development, Vol. 22, Issue 8 https://doi.org/10.1101/gad.463708	journal	March 2008
A Systems Approach to Mapping DNA Damage Response Pathways Workman, C. T. Science, Vol. 312, Issue 5776 https://doi.org/10.1126/science.1122088	journal	May 2006
Adapting Proteostasis for Disease Intervention Balch, William E.; Morimoto, Richard I.; Dillin, Andrew Science, Vol. 319, Issue 5865 https://doi.org/10.1126/science.1141448	journal	February 2008
Synchronizing Nuclear Import of Ribosomal Proteins with Ribosome Assembly Kressler, D.; Bange, G.; Ogawa, Y. Science, Vol. 338, Issue 6107 https://doi.org/10.1126/science.1226960	journal	November 2012
Ribosomopathies: There’s strength in numbers Mills, Eric W.; Green, Rachel Science, Vol. 358, Issue 6363 https://doi.org/10.1126/science.aan2755	journal	November 2017
MitoCPR—A surveillance pathway that protects mitochondria in response to protein import stress Weidberg, Hilla; Amon, Angelika Science, Vol. 360, Issue 6385 https://doi.org/10.1126/science.aan4146	journal	April 2018
Reduction in Ribosomal Protein Synthesis Is Sufficient To Explain Major Effects on Ribosome Production after Short-Term TOR Inactivation in Saccharomyces cerevisiae Reiter, A.; Steinbauer, R.; Philippi, A. Molecular and Cellular Biology, Vol. 31, Issue 4 https://doi.org/10.1128/MCB.01227-10	journal	December 2010
Diazaborine Treatment of Yeast Cells Inhibits Maturation of the 60S Ribosomal Subunit Pertschy, B.; Zisser, G.; Schein, H. Molecular and Cellular Biology, Vol. 24, Issue 14 https://doi.org/10.1128/MCB.24.14.6476-6487.2004	journal	June 2004
Effect of RP51 gene dosage alterations on ribosome synthesis in Saccharomyces cerevisiae. Abovich, N.; Gritz, L.; Tung, L. Molecular and Cellular Biology, Vol. 5, Issue 12 https://doi.org/10.1128/MCB.5.12.3429	journal	December 1985
Effect of RP51 gene dosage alterations on ribosome synthesis in Saccharomyces cerevisiae Abovich, N.; Gritz, L.; Tung, L. Molecular and Cellular Biology, Vol. 5, Issue 12 https://doi.org/10.1128/mcb.5.12.3429-3435.1985	journal	December 1985
Ribosomopathies: human disorders of ribosome dysfunction Narla, Anupama; Ebert, Benjamin L. Blood, Vol. 115, Issue 16 https://doi.org/10.1182/blood-2009-10-178129	journal	April 2010
Ribosome biogenesis in the yeast Saccharomyces cerevisiae. Woolford, John; Baserga, Susan J. Carnegie Mellon University https://doi.org/10.1184/r1/6104207	text	January 2013
Ribosome biogenesis in the yeast Saccharomyces cerevisiae. Woolford, John; Baserga, Susan J. Carnegie Mellon University https://doi.org/10.1184/r1/6104207.v1	text	January 2013
Datura genome reveals duplications of psychoactive alkaloid biosynthetic genes and high mutation rate following tissue culture Rajewski, Alex; Carter-House, Derreck; Stajich, Jason BMC Genomics, Vol. 22, Issue 1 https://doi.org/10.1186/s12864-021-07489-2	journal	March 2021
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 Love, Michael I.; Huber, Wolfgang; Anders, Simon Genome Biology, Vol. 15, Issue 12 https://doi.org/10.1186/s13059-014-0550-8	journal	December 2014
Patterns of ribosomal protein expression specify normal and malignant human cells Guimaraes, Joao C.; Zavolan, Mihaela Genome Biology, Vol. 17, Issue 1 https://doi.org/10.1186/s13059-016-1104-z	journal	November 2016
Compartment-specific perturbation of protein handling activates genes encoding mitochondrial chaperones Yoneda, T. Journal of Cell Science, Vol. 117, Issue 18 https://doi.org/10.1242/jcs.01275	journal	August 2004
Many Ribosomal Protein Genes Are Cancer Genes in Zebrafish Amsterdam, Adam; Sadler, Kirsten C.; Lai, Kevin PLoS Biology, Vol. 2, Issue 5 https://doi.org/10.1371/journal.pbio.0020139	journal	May 2004
Widespread Protein Aggregation as an Inherent Part of Aging in C. elegans David, Della C.; Ollikainen, Noah; Trinidad, Jonathan C. PLoS Biology, Vol. 8, Issue 8 https://doi.org/10.1371/journal.pbio.1000450	journal	August 2010
Long Noncoding RNAs Promote Transcriptional Poising of Inducible Genes Cloutier, Sara C.; Wang, Siwen; Ma, Wai Kit PLoS Biology, Vol. 11, Issue 11 https://doi.org/10.1371/journal.pbio.1001715	journal	November 2013
Natural Variation in Preparation for Nutrient Depletion Reveals a Cost–Benefit Tradeoff Wang, Jue; Atolia, Esha; Hua, Bo PLOS Biology, Vol. 13, Issue 1 https://doi.org/10.1371/journal.pbio.1002041	journal	January 2015
Tor1 and CK2 kinases control a switch between alternative ribosome biogenesis pathways in a growth-dependent manner Kos-Braun, Isabelle C.; Jung, Ilona; Koš, Martin PLOS Biology, Vol. 15, Issue 3 https://doi.org/10.1371/journal.pbio.2000245	journal	March 2017
The Type II Hsp40 Sis1 Cooperates with Hsp70 and the E3 Ligase Ubr1 to Promote Degradation of Terminally Misfolded Cytosolic Protein Summers, Daniel W.; Wolfe, Katie J.; Ren, Hong Yu PLoS ONE, Vol. 8, Issue 1 https://doi.org/10.1371/journal.pone.0052099	journal	January 2013
TORC1 Promotes Phosphorylation of Ribosomal Protein S6 via the AGC Kinase Ypk3 in Saccharomyces cerevisiae González, Asier; Shimobayashi, Mitsugu; Eisenberg, Tobias PLOS ONE, Vol. 10, Issue 3 https://doi.org/10.1371/journal.pone.0120250	journal	March 2015
Compartment‐specific aggregases direct distinct nuclear and cytoplasmic aggregate deposition Miller, Stephanie BM; Ho, Chi‐Ting; Winkler, Juliane The EMBO Journal, Vol. 34, Issue 6 https://doi.org/10.15252/embj.201489524	journal	December 2014
Restricted access: spatial sequestration of damaged proteins during stress and aging Hill, Sandra Malmgren; Hanzén, Sarah; Nyström, Thomas EMBO reports, Vol. 18, Issue 3 https://doi.org/10.15252/embr.201643458	journal	February 2017
Disruption of Rpn4-Induced Proteasome Expression in Saccharomyces cerevisiae Reduces Cell Viability Under Stressed Conditions Wang, Xiaogang; Xu, Haiming; Ju, Donghong Genetics, Vol. 180, Issue 4 https://doi.org/10.1534/genetics.108.094524	journal	October 2008
Proteasomal Degradation of Rpn4 in Saccharomyces cerevisiae Is Critical for Cell Viability Under Stressed Conditions Wang, Xiaogang; Xu, Haiming; Ha, Seung-Wook Genetics, Vol. 184, Issue 2 https://doi.org/10.1534/genetics.109.112227	journal	November 2009
Ribosome Deficiency Protects Against ER Stress in Saccharomyces cerevisiae Steffen, Kristan K.; McCormick, Mark A.; Pham, Kim M. Genetics, Vol. 191, Issue 1 https://doi.org/10.1534/genetics.111.136549	journal	February 2012
Ribosome Biogenesis in the Yeast Saccharomyces cerevisiae Woolford, John L.; Baserga, Susan J. Genetics, Vol. 195, Issue 3 https://doi.org/10.1534/genetics.113.153197	journal	November 2013
The Type II Hsp40 Sis1 Cooperates with Hsp70 and the E3 Ligase Ubr1 to Promote Degradation of Terminally Misfolded Cytosolic Protein M., Cyr, Douglas; Yu, Ren, Hong; J., Wolfe, Katie The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/11fy-1111	text	January 2013
Defining the limits: Protein aggregation and toxicity in vivo Holmes, William M.; Klaips, Courtney L.; Serio, Tricia R. Critical Reviews in Biochemistry and Molecular Biology, Vol. 49, Issue 4 https://doi.org/10.3109/10409238.2014.914151	journal	March 2014
Role of ribosomal protein mutations in tumor development (Review) Goudarzi, Kaveh M.; LindstrÖM, Mikael S. International Journal of Oncology, Vol. 48, Issue 4 https://doi.org/10.3892/ijo.2016.3387	journal	February 2016
Nucleolar stress with and without p53 James, Allison; Wang, Yubo; Raje, Himanshu Nucleus, Vol. 5, Issue 5 https://doi.org/10.4161/nucl.32235	journal	August 2014
Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast Dephoure, Noah; Hwang, Sunyoung; O'Sullivan, Ciara eLife, Vol. 3 https://doi.org/10.7554/eLife.03023	journal	July 2014
Paradoxical resistance of multiple myeloma to proteasome inhibitors by decreased levels of 19S proteasomal subunits Acosta-Alvear, Diego; Cho, Min Y.; Wild, Thomas eLife, Vol. 4 https://doi.org/10.7554/eLife.08153	journal	September 2015
Compromising the 19S proteasome complex protects cells from reduced flux through the proteasome Tsvetkov, Peter; Mendillo, Marc L.; Zhao, Jinghui eLife, Vol. 4 https://doi.org/10.7554/eLife.08467	journal	September 2015
Dynamic control of Hsf1 during heat shock by a chaperone switch and phosphorylation Zheng, Xu; Krakowiak, Joanna; Patel, Nikit eLife, Vol. 5 https://doi.org/10.7554/eLife.18638	journal	November 2016
A conserved quality-control pathway that mediates degradation of unassembled ribosomal proteins Sung, Min-Kyung; Porras-Yakushi, Tanya R.; Reitsma, Justin M. eLife, Vol. 5 https://doi.org/10.7554/eLife.19105	journal	August 2016
Principles of cellular resource allocation revealed by condition-dependent proteome profiling Metzl-Raz, Eyal; Kafri, Moshe; Yaakov, Gilad eLife, Vol. 6 https://doi.org/10.7554/eLife.28034	journal	August 2017

Cited By (4)

rRNA expansion segment 27Lb modulates the factor recruitment capacity of the yeast ribosome and shapes the proteome Shankar, Vaishnavi; Rauscher, Robert; Reuther, Julia Nucleic Acids Research, Vol. 48, Issue 6 https://doi.org/10.1093/nar/gkaa003	journal	January 2020
Dosage compensation plans: protein aggregation provides additional insurance against aneuploidy Samant, Rahul S.; Masto, Vincent B.; Frydman, Judith Genes & Development, Vol. 33, Issue 15-16 https://doi.org/10.1101/gad.329383.119	journal	August 2019
Cytoplasmic protein misfolding titrates Hsp70 to activate nuclear Hsf1 Masser, Anna E.; Kang, Wenjing; Roy, Joydeep eLife, Vol. 8 https://doi.org/10.7554/elife.47791	journal	September 2019
rRNA expansion segment 27Lb modulates the factor recruitment capacity of the yeast ribosome and shapes the proteome. Shankar, Vaishnavi; Rauscher, Robert; Reuther, Julia Oxford University Press https://doi.org/10.7892/boris.139713	text	January 2020

Similar Records

Nop-7-associated 2 (NSA2) is required for ribosome biogenesis and protein synthesis

Journal Article · Mon Oct 15 00:00:00 EDT 2018 · Biochemical and Biophysical Research Communications · OSTI ID:23107822

The DEAD-box ATPase Dbp10/DDX54 initiates peptidyl transferase center formation during 60S ribosome biogenesis

Journal Article · Tue Apr 16 20:00:00 EDT 2024 · Nature Communications · OSTI ID:2471669

Structure of ERA in Complex with the 3 End of 16s rRNBA Implications for Ribosome Biogenesis

Journal Article · Wed Dec 31 23:00:00 EST 2008 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:980553

Related Subjects

59 BASIC BIOLOGICAL SCIENCES

Proteotoxicity from aberrant ribosome biogenesis compromises cell fitness

Citation Formats

References (112)

Cited By (4)

Similar Records

Related Subjects