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Systematic quantitative analysis of ribosome inventory during nutrient stress

Author

Listed:
  • Heeseon An

    (Blavatnik Institute, Harvard Medical School)

  • Alban Ordureau

    (Blavatnik Institute, Harvard Medical School)

  • Maria Körner

    (Blavatnik Institute, Harvard Medical School
    University of Würzburg)

  • Joao A. Paulo

    (Blavatnik Institute, Harvard Medical School)

  • J. Wade Harper

    (Blavatnik Institute, Harvard Medical School)

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.

Suggested Citation

  • Heeseon An & Alban Ordureau & Maria Körner & Joao A. Paulo & J. Wade Harper, 2020. "Systematic quantitative analysis of ribosome inventory during nutrient stress," Nature, Nature, vol. 583(7815), pages 303-309, July.
  • Handle: RePEc:nat:nature:v:583:y:2020:i:7815:d:10.1038_s41586-020-2446-y
    DOI: 10.1038/s41586-020-2446-y
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    Cited by:

    1. Judith Dönig & Hannah Mende & Jimena Davila Gallesio & Kristina Wagner & Paul Hotz & Kathrin Schunck & Tanja Piller & Soraya Hölper & Sara Uhan & Manuel Kaulich & Matthias Wirth & Ulrich Keller & Geor, 2023. "Characterization of nucleolar SUMO isopeptidases unveils a general p53-independent checkpoint of impaired ribosome biogenesis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Shiyan Liu & Mutian Chen & Yichang Wang & Yuqing Lei & Ting Huang & Yabin Zhang & Sin Man Lam & Huihui Li & Shiqian Qi & Jia Geng & Kefeng Lu, 2023. "The ER calcium channel Csg2 integrates sphingolipid metabolism with autophagy," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Arthur Louche & Amandine Blanco & Thais Lourdes Santos Lacerda & Lison Cancade-Veyre & Claire Lionnet & Célia Bergé & Monica Rolando & Frédérique Lembo & Jean-Paul Borg & Carmen Buchrieser & Masami Na, 2023. "Brucella effectors NyxA and NyxB target SENP3 to modulate the subcellular localisation of nucleolar proteins," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Xiang Li & Mengjiao Wang & Timo Denk & Robert Buschauer & Yi Li & Roland Beckmann & Jingdong Cheng, 2024. "Structural basis for differential inhibition of eukaryotic ribosomes by tigecycline," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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