A ribosome assembly stress response regulates transcription to maintain proteome homeostasis

  1. Benjamin Albert
  2. Isabelle C Kos-Braun
  3. Anthony K Henras
  4. Christophe Dez
  5. Maria Paula Rueda
  6. Xu Zhang
  7. Olivier Gadal
  8. Martin Kos
  9. David Shore  Is a corresponding author
  1. University of Geneva, Switzerland
  2. Heidelberg University, Germany
  3. Université Paul Sabatier, France

Abstract

Ribosome biogenesis is a complex and energy-demanding process requiring tight coordination of ribosomal RNA (rRNA) and ribosomal protein (RP) production. Given the extremely high level of RP synthesis in rapidly growing cells, alteration of any step in the ribosome assembly process may impact growth by leading to proteotoxic stress. Although the transcription factor Hsf1 has emerged as a central regulator of proteostasis, how its activity is coordinated with ribosome biogenesis is unknown. Here we show that arrest of ribosome biogenesis in the budding yeast S. cerevisiae triggers rapid activation of a highly specific stress pathway that coordinately up-regulates Hsf1 target genes and down-regulates RP genes. Activation of Hsf1 target genes requires neo-synthesis of RPs, which accumulate in an insoluble fraction and presumably titrate a negative regulator of Hsf1, the Hsp70 chaperone. RP aggregation is also coincident with that of the RP gene activator Ifh1, a transcription factor that is rapidly released from RP gene promoters. Our data support a model in which the levels of newly-synthetized RPs, imported into the nucleus but not yet assembled into ribosomes, work to continuously balance Hsf1 and Ifh1 activity, thus guarding against proteotoxic stress during ribosome assembly.

Data availability

Sequencing data have been deposited in GEO under accession code GSE125226. Previously published data were used from Supplementary file 3 of Sung et al. 2016, eLife (https://elifesciences.org/articles/19105/figures#SD7-data) and Supplemental Table S3 from Sung et al. 2016, Mol Biol Cell (supp_E16-05-0290v1_mc-E16-05-0290-s06.xlsx).

The following data sets were generated

Article and author information

Author details

  1. Benjamin Albert

    Department of Molecular Biology, University of Geneva, Geneva, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  2. Isabelle C Kos-Braun

    Biochemistry Center (BZH), Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Anthony K Henras

    Centre de Biologie Intégrative, Université Paul Sabatier, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Christophe Dez

    Centre de Biologie Intégrative, Université Paul Sabatier, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Maria Paula Rueda

    Department of Molecular Biology, University of Geneva, Geneva, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Xu Zhang

    Department of Molecular Biology, University of Geneva, Geneva, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  7. Olivier Gadal

    Centre de Biologie Intégrative, Université Paul Sabatier, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9421-0831
  8. Martin Kos

    Biochemistry Centre (BZH), Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3337-9681
  9. David Shore

    Department of Molecular Biology, University of Geneva, Geneva, Switzerland
    For correspondence
    David.Shore@unige.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9859-143X

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_170153)

  • David Shore

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Alan G Hinnebusch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States

Version history

  1. Received: January 9, 2019
  2. Accepted: May 23, 2019
  3. Accepted Manuscript published: May 24, 2019 (version 1)
  4. Version of Record published: June 17, 2019 (version 2)

Copyright

© 2019, Albert et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Benjamin Albert
  2. Isabelle C Kos-Braun
  3. Anthony K Henras
  4. Christophe Dez
  5. Maria Paula Rueda
  6. Xu Zhang
  7. Olivier Gadal
  8. Martin Kos
  9. David Shore
(2019)
A ribosome assembly stress response regulates transcription to maintain proteome homeostasis
eLife 8:e45002.
https://doi.org/10.7554/eLife.45002

Share this article

https://doi.org/10.7554/eLife.45002

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