GC content shapes mRNA storage and decay in human cells

  1. Maïté Courel
  2. Yves Clément
  3. Clémentine Bossevain
  4. Dominika Foretek
  5. Olivia Vidal Cruchez
  6. Zhou Yi
  7. Marianne Bénard
  8. Marie‐Noëlle Benassy
  9. Michel Kress
  10. Caroline Vindry
  11. Michèle Ernoult-Lange
  12. Christophe Antoniewski
  13. Antonin Morillon
  14. Patrick Brest
  15. Arnaud Hubstenberger
  16. Hugues Roest Crollius
  17. Nancy Standart
  18. Dominique Weil  Is a corresponding author
  1. Centre National de la Recherche Scientifique (CNRS), Sorbonne Université, France
  2. Ecole Normale Supérieure, France
  3. Institut Curie, France
  4. Université Côte d'Azur, CNRS, INSERM, France
  5. University of Cambridge, United Kingdom

Abstract

mRNA translation and decay appear often intimately linked although the rules of this interplay are poorly understood. In this study, we combined our recent P-body transcriptome with transcriptomes obtained following silencing of broadly acting mRNA decay and repression factors, and with available CLIP and related data. This revealed the central role of GC content in mRNA fate, in terms of P-body localization, mRNA translation and mRNA stability: P-bodies contain mostly AU-rich mRNAs, which have a particular codon usage associated with a low protein yield; AU-rich and GC-rich transcripts tend to follow distinct decay pathways; and the targets of sequence-specific RBPs and miRNAs are also biased in terms of GC content. Altogether, these results suggest an integrated view of post-transcriptional control in human cells where most translation regulation is dedicated to inefficiently translated AU-rich mRNAs, whereas control at the level of 5' decay applies to optimally translated GC-rich mRNAs.

Data availability

RNA-Seq gene data have been deposited in SRA under accession codes E-MTAB-4091 for the polysome profiling after DDX6 silencing, E-MTAB-5577 for the transcriptome after PAT1B silencing, and E-MTAB-5477 for the PB transcriptome, all in HEK293 cells.RNA-Seq gene data have been deposited in GEO under accession codes GSE115471 and GSE114605 for the transcriptome after XRN1 silencing in HeLa and HCT116 cells, respectively.ENCODE datasets are available at https://www.encodeproject.org under accession codes ENCSR893EFU for the DDX6 eClip experiment, and ENCSR109IQO for the transcriptome after DDX6 silencing in K562 cells.All data generated or analyzed during this study are included in the Supplementary file 1.

The following data sets were generated

Article and author information

Author details

  1. Maïté Courel

    Laboratory of Developmental Biology, Institut de Biologie Paris Seine, Centre National de la Recherche Scientifique (CNRS), Sorbonne Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Yves Clément

    Institut de Biologie de l'ENS, Ecole Normale Supérieure, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5932-9412
  3. Clémentine Bossevain

    Laboratory of Developmental Biology, Institut de Biologie Paris Seine, Centre National de la Recherche Scientifique (CNRS), Sorbonne Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Dominika Foretek

    Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Olivia Vidal Cruchez

    IRCAN, FHU‐OncoAge, Université Côte d'Azur, CNRS, INSERM, Nice, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Zhou Yi

    iBV, Université Côte d'Azur, CNRS, INSERM, Nice, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Marianne Bénard

    Laboratory of Developmental Biology, Institut de Biologie Paris Seine, Centre National de la Recherche Scientifique (CNRS), Sorbonne Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Marie‐Noëlle Benassy

    Laboratory of Developmental Biology, Institut de Biologie Paris Seine, Centre National de la Recherche Scientifique (CNRS), Sorbonne Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Michel Kress

    Laboratory of Developmental Biology, Institut de Biologie Paris Seine, Centre National de la Recherche Scientifique (CNRS), Sorbonne Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Caroline Vindry

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Michèle Ernoult-Lange

    Laboratory of Developmental Biology, Institut de Biologie Paris Seine, Centre National de la Recherche Scientifique (CNRS), Sorbonne Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  12. Christophe Antoniewski

    ARTbio Bioinformatics Analysis Facility, Centre National de la Recherche Scientifique (CNRS), Sorbonne Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7709-2116
  13. Antonin Morillon

    Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0575-5264
  14. Patrick Brest

    IRCAN, FHU‐OncoAge, Université Côte d'Azur, CNRS, INSERM, Nice, France
    Competing interests
    The authors declare that no competing interests exist.
  15. Arnaud Hubstenberger

    iBV, Université Côte d'Azur, CNRS, INSERM, Nice, France
    Competing interests
    The authors declare that no competing interests exist.
  16. Hugues Roest Crollius

    Institut de Biologie de l'ENS, Ecole Normale Supérieure, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8209-173X
  17. Nancy Standart

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  18. Dominique Weil

    Laboratory of Developmental Biology, Institut de Biologie Paris Seine, Centre National de la Recherche Scientifique (CNRS), Sorbonne Université, Paris, France
    For correspondence
    dominique.weil@upmc.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7630-1772

Funding

Association pour la Recherche sur le Cancer (Subvention Fixe)

  • Dominique Weil

Agence Nationale de la Recherche (ANR-14-CE09-0013-01)

  • Dominique Weil

European Research Council (DARK consolidator grant)

  • Antonin Morillon

Agence Nationale de la Recherche (ANR-11-LABX-0028-01)

  • Antonin Morillon

Canceropole PACA

  • Patrick Brest

Biotechnology and Biological Sciences Research Council

  • Nancy Standart

Newton Trust and Foundation Wiener

  • Nancy Standart

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

Copyright

© 2019, Courel 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. Maïté Courel
  2. Yves Clément
  3. Clémentine Bossevain
  4. Dominika Foretek
  5. Olivia Vidal Cruchez
  6. Zhou Yi
  7. Marianne Bénard
  8. Marie‐Noëlle Benassy
  9. Michel Kress
  10. Caroline Vindry
  11. Michèle Ernoult-Lange
  12. Christophe Antoniewski
  13. Antonin Morillon
  14. Patrick Brest
  15. Arnaud Hubstenberger
  16. Hugues Roest Crollius
  17. Nancy Standart
  18. Dominique Weil
(2019)
GC content shapes mRNA storage and decay in human cells
eLife 8:e49708.
https://doi.org/10.7554/eLife.49708

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https://doi.org/10.7554/eLife.49708