Decapping factor Dcp2 controls mRNA abundance and translation to adjust metabolism and filamentation to nutrient availability

  1. Anil Kumar Vijjamarri
  2. Xiao Niu
  3. Matthew D Vandermeulen
  4. Chisom Onu
  5. Fan Zhang
  6. Hongfang Qiu
  7. Neha Gupta
  8. Swati Gaikwad
  9. Miriam L Greenberg
  10. Paul J Cullen
  11. Zhenguo Lin
  12. Alan G Hinnebusch  Is a corresponding author
  1. Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States
  2. Saint Louis University, United States
  3. State University of New York, United States
  4. Wayne State University, United States

Abstract

Degradation of most yeast mRNAs involves decapping by Dcp1/Dcp2. DEAD-box protein Dhh1 has been implicated as an activator of decapping, in coupling codon non-optimality to enhanced degradation, and as a translational repressor, but its functions in cells are incompletely understood. RNA-Seq analyses coupled with CAGE sequencing of all capped mRNAs revealed increased abundance of hundreds of mRNAs in dcp2Δ cells that appears to result directly from impaired decapping rather than elevated transcription. Interestingly, only a subset of mRNAs requires Dhh1 for targeting by Dcp2, and also generally requires the other decapping activators Pat1, Edc3 or Scd6; whereas most of the remaining transcripts utilize NMD factors for Dcp2-mediated turnover. Neither inefficient translation initiation nor stalled elongation appears to be a major driver of Dhh1-enhanced mRNA degradation. Surprisingly, ribosome profiling revealed that dcp2Δ confers widespread changes in relative translational efficiencies (TEs) that generally favor well-translated mRNAs. Because ribosome biogenesis is reduced while capped mRNA abundance is increased by dcp2&Delta, we propose that an increased ratio of mRNA to ribosomes increases competition among mRNAs for limiting ribosomes to favor efficiently translated mRNAs in dcp2Δ cells. Interestingly, genes involved in respiration or utilization of alternative carbon or nitrogen sources are up-regulated, and both mitochondrial function and cell filamentation are elevated in dcp2Δ cells, suggesting that decapping sculpts gene expression post-transcriptionally to fine-tune metabolic pathways and morphological transitions according to nutrient availability.

Data availability

Sequencing data have been deposited in GEO under accession codes GSE220578. All other data generated or analysed during this study are included in the manuscript and supporting files; Source Data files have been provided for all figures.

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Article and author information

Author details

  1. Anil Kumar Vijjamarri

    Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    No competing interests declared.
  2. Xiao Niu

    Department of Biology, Saint Louis University, Saint Louis, United States
    Competing interests
    No competing interests declared.
  3. Matthew D Vandermeulen

    Department of Biological Sciences, State University of New York, Buffalo, United States
    Competing interests
    No competing interests declared.
  4. Chisom Onu

    Department of Biological Sciences, Wayne State University, Detroit, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3338-5141
  5. Fan Zhang

    Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    No competing interests declared.
  6. Hongfang Qiu

    Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    No competing interests declared.
  7. Neha Gupta

    Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    No competing interests declared.
  8. Swati Gaikwad

    Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1438-9497
  9. Miriam L Greenberg

    Department of Biological Sciences, Wayne State University, Detroit, United States
    Competing interests
    No competing interests declared.
  10. Paul J Cullen

    Department of Biological Sciences, State University of New York, Buffalo, United States
    Competing interests
    No competing interests declared.
  11. Zhenguo Lin

    Department of Biological Sciences, Saint Louis University, Saint Louis, United States
    Competing interests
    No competing interests declared.
  12. Alan G Hinnebusch

    Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States
    For correspondence
    ahinnebusch@nih.gov
    Competing interests
    Alan G Hinnebusch, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1627-8395

Funding

National Heart, Lung, and Blood Institute (HL117880)

  • Miriam L Greenberg

National Heart, Lung, and Blood Institute (HL117880)

  • Chisom Onu

National Institute of General Medical Sciences (GM098629)

  • Matthew D Vandermeulen

National Institute of General Medical Sciences (GM098629)

  • Paul J Cullen

National Science Foundation (1951332)

  • Xiao Niu

National Science Foundation (1951332)

  • Zhenguo Lin

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

Reviewing Editor

  1. Timothy W Nilsen, Case Western Reserve University, United States

Version history

  1. Received: December 13, 2022
  2. Preprint posted: January 5, 2023 (view preprint)
  3. Accepted: June 1, 2023
  4. Accepted Manuscript published: June 2, 2023 (version 1)
  5. Version of Record published: June 22, 2023 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Anil Kumar Vijjamarri
  2. Xiao Niu
  3. Matthew D Vandermeulen
  4. Chisom Onu
  5. Fan Zhang
  6. Hongfang Qiu
  7. Neha Gupta
  8. Swati Gaikwad
  9. Miriam L Greenberg
  10. Paul J Cullen
  11. Zhenguo Lin
  12. Alan G Hinnebusch
(2023)
Decapping factor Dcp2 controls mRNA abundance and translation to adjust metabolism and filamentation to nutrient availability
eLife 12:e85545.
https://doi.org/10.7554/eLife.85545

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