Rvb1/Rvb2 proteins couple transcription and translation during glucose starvation

  1. Yang S Chen
  2. Wanfu Hou
  3. Sharon Tracy
  4. Alex T Harvey
  5. Vince Harjono
  6. Fan Xu
  7. James J Moresco
  8. John R Yates III
  9. Brian M Zid  Is a corresponding author
  1. University of California, San Diego, United States
  2. Scripps Research Institute, United States
  3. University of California San Diego, United States

Abstract

During times of unpredictable stress, organisms must adapt their gene expression to maximize survival. Along with changes in transcription, one conserved means of gene regulation during conditions that quickly represses translation is the formation of cytoplasmic phase-separated mRNP granules such as P-bodies and stress granules. Previously, we identified that distinct steps in gene expression can be coupled during glucose starvation as promoter sequences in the nucleus are able to direct the subcellular localization and translatability of mRNAs in the cytosol. Here, we report that Rvb1 and Rvb2, conserved ATPase proteins implicated as protein assembly chaperones and chromatin remodelers, were enriched at the promoters and mRNAs of genes involved in alternative glucose metabolism pathways that we previously found to be transcriptionally upregulated but translationally downregulated during glucose starvation in yeast. Engineered Rvb1/Rvb2-binding on mRNAs was sufficient to sequester mRNAs into mRNP granules and repress their translation. Additionally, this Rvb-tethering to the mRNA drove further transcriptional upregulation of the target genes. Further we found that depletion of Rvb2 caused decreased alternative glucose metabolism gene mRNA induction, but upregulation of protein synthesis during glucose starvation. Overall, our results point to Rvb1/Rvb2 coupling transcription, mRNA granular localization, and translatability of mRNAs during glucose starvation. This Rvb-mediated rapid gene regulation could potentially serve as an efficient recovery plan for cells after stress removal.

Data availability

ChIP-sequencing reads were deposited at GEO. The raw files and analyzed ChIP-seq enrichment data generated in this study is available at GEO: GSE184473. Ribosome profiling sequencing reads are deposited at GEO: GSE200491. CoTrIP plasmids can be obtained through Addgene - 178303, 178304, 178306. Further information and requests for resources and reagents should be directed to and will be fulfilled by the corresponding contact, B.M.Z. (zid@ucsd.edu).

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Yang S Chen

    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3174-091X
  2. Wanfu Hou

    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Sharon Tracy

    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Alex T Harvey

    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Vince Harjono

    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Fan Xu

    Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0041-4276
  7. James J Moresco

    Department of Chemical Physiology, Scripps Research Institute, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. John R Yates III

    Scripps Research Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5267-1672
  9. Brian M Zid

    Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, United States
    For correspondence
    zid@ucsd.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1876-2479

Funding

National Institute of General Medical Sciences (R35GM128798)

  • Brian M Zid

National Institute of General Medical Sciences (P41GM103533)

  • James J Moresco
  • John R Yates III

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

Publication history

  1. Preprint posted: October 18, 2021 (view preprint)
  2. Received: February 4, 2022
  3. Accepted: September 13, 2022
  4. Accepted Manuscript published: September 15, 2022 (version 1)
  5. Version of Record published: October 4, 2022 (version 2)

Copyright

© 2022, Chen 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. Yang S Chen
  2. Wanfu Hou
  3. Sharon Tracy
  4. Alex T Harvey
  5. Vince Harjono
  6. Fan Xu
  7. James J Moresco
  8. John R Yates III
  9. Brian M Zid
(2022)
Rvb1/Rvb2 proteins couple transcription and translation during glucose starvation
eLife 11:e76965.
https://doi.org/10.7554/eLife.76965
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