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Systematic quantitative analysis of ribosome inventory during nutrient stress.
Nature. 2020 07; 583(7815):303-309.Nat

Abstract

Mammalian cells reorganize their proteomes in response to nutrient stress through translational suppression and degradative mechanisms using the proteasome and autophagy systems1,2. Ribosomes are central targets of this response, as they are responsible for translation and subject to lysosomal turnover during nutrient stress3-5. The abundance of ribosomal (r)-proteins (around 6% of the proteome; 107 copies per cell)6,7 and their high arginine and lysine content has led to the hypothesis that they are selectively used as a source of basic amino acids during nutrient stress through autophagy4,7. However, the relative contributions of translational and degradative mechanisms to the control of r-protein abundance during acute stress responses is poorly understood, as is the extent to which r-proteins are used to generate amino acids when specific building blocks are limited7. Here, we integrate quantitative global translatome and degradome proteomics8 with genetically encoded Ribo-Keima5 and Ribo-Halo reporters to interrogate r-protein homeostasis with and without active autophagy. In conditions of acute nutrient stress, cells strongly suppress the translation of r-proteins, but, notably, r-protein degradation occurs largely through non-autophagic pathways. Simultaneously, the decrease in r-protein abundance is compensated for by a reduced dilution of pre-existing ribosomes and a reduction in cell volume, thereby maintaining the density of ribosomes within single cells. Withdrawal of basic or hydrophobic amino acids induces translational repression without differential induction of ribophagy, indicating that ribophagy is not used to selectively produce basic amino acids during acute nutrient stress. We present a quantitative framework that describes the contributions of biosynthetic and degradative mechanisms to r-protein abundance and proteome remodelling in conditions of nutrient stress.

Authors+Show Affiliations

Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. Department of Biochemistry, University of Würzburg, Würzburg, Germany.Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. wade_harper@hms.harvard.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32612236

Citation

An, Heeseon, et al. "Systematic Quantitative Analysis of Ribosome Inventory During Nutrient Stress." Nature, vol. 583, no. 7815, 2020, pp. 303-309.
An H, Ordureau A, Körner M, et al. Systematic quantitative analysis of ribosome inventory during nutrient stress. Nature. 2020;583(7815):303-309.
An, H., Ordureau, A., Körner, M., Paulo, J. A., & Harper, J. W. (2020). Systematic quantitative analysis of ribosome inventory during nutrient stress. Nature, 583(7815), 303-309. https://doi.org/10.1038/s41586-020-2446-y
An H, et al. Systematic Quantitative Analysis of Ribosome Inventory During Nutrient Stress. Nature. 2020;583(7815):303-309. PubMed PMID: 32612236.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Systematic quantitative analysis of ribosome inventory during nutrient stress. AU - An,Heeseon, AU - Ordureau,Alban, AU - Körner,Maria, AU - Paulo,Joao A, AU - Harper,J Wade, Y1 - 2020/07/01/ PY - 2020/02/02/received PY - 2020/05/07/accepted PY - 2021/01/01/pmc-release PY - 2020/7/3/pubmed PY - 2020/8/11/medline PY - 2020/7/3/entrez SP - 303 EP - 309 JF - Nature JO - Nature VL - 583 IS - 7815 N2 - Mammalian cells reorganize their proteomes in response to nutrient stress through translational suppression and degradative mechanisms using the proteasome and autophagy systems1,2. Ribosomes are central targets of this response, as they are responsible for translation and subject to lysosomal turnover during nutrient stress3-5. The abundance of ribosomal (r)-proteins (around 6% of the proteome; 107 copies per cell)6,7 and their high arginine and lysine content has led to the hypothesis that they are selectively used as a source of basic amino acids during nutrient stress through autophagy4,7. However, the relative contributions of translational and degradative mechanisms to the control of r-protein abundance during acute stress responses is poorly understood, as is the extent to which r-proteins are used to generate amino acids when specific building blocks are limited7. Here, we integrate quantitative global translatome and degradome proteomics8 with genetically encoded Ribo-Keima5 and Ribo-Halo reporters to interrogate r-protein homeostasis with and without active autophagy. In conditions of acute nutrient stress, cells strongly suppress the translation of r-proteins, but, notably, r-protein degradation occurs largely through non-autophagic pathways. Simultaneously, the decrease in r-protein abundance is compensated for by a reduced dilution of pre-existing ribosomes and a reduction in cell volume, thereby maintaining the density of ribosomes within single cells. Withdrawal of basic or hydrophobic amino acids induces translational repression without differential induction of ribophagy, indicating that ribophagy is not used to selectively produce basic amino acids during acute nutrient stress. We present a quantitative framework that describes the contributions of biosynthetic and degradative mechanisms to r-protein abundance and proteome remodelling in conditions of nutrient stress. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/32612236/Systematic_quantitative_analysis_of_ribosome_inventory_during_nutrient_stress L2 - https://doi.org/10.1038/s41586-020-2446-y DB - PRIME DP - Unbound Medicine ER -