Vasohibin1, a new mouse cardiomyocyte IRES trans-acting factor that regulates translation during early hypoxia

  1. Fransky Hantelys
  2. Anne-Claire Godet
  3. Florian David
  4. Florence Tatin
  5. Edith Renaud-Gabardos
  6. Françoise Pujol
  7. Leila H Diallo
  8. Isabelle Ader
  9. Laetitia Ligat
  10. Anthony K Henras
  11. Yasufumi Sato
  12. Angelo Parini
  13. Eric Lacazette
  14. Barbara Garmy-Susini
  15. Anne-Catherine Prats  Is a corresponding author
  1. Inserm UMR 1048, France
  2. Inserm U1031, France
  3. Inserm UMR 1037, France
  4. Université Paul Sabatier, France
  5. Tohoku Universtiy, Japan

Abstract

Hypoxia, a major inducer of angiogenesis, triggers major changes of gene expression at the transcriptional level. Furthermore, global protein synthesis is blocked while internal ribosome entry sites (IRES) allow specific mRNAs to be translated. Here we report the transcriptome and translatome signatures of (lymph)angiogenic genes in hypoxic HL-1 mouse cardiomyocytes: most genes are induced at the translatome level, including all IRES-containing mRNAs. Our data reveal activation of (lymph)angiogenic factor mRNA IRESs in early hypoxia. We identify vasohibin1 (VASH1) as an IRES trans-acting factor (ITAF) able to bind RNA and to activate the FGF1 IRES in hypoxia while it tends to inhibit several IRESs in normoxia. VASH1 depletion has also a wide impact on the translatome of (lymph)angiogenesis genes, suggesting that this protein can regulate translation positively or negatively in early hypoxia. Translational control thus appears as a pivotal process to trigger new vessel formation in ischemic heart.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Lentivector plasmid complete maps and sequences are available on Dryad.

The following data sets were generated

Article and author information

Author details

  1. Fransky Hantelys

    I2MC, Inserm UMR 1048, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Anne-Claire Godet

    I2MC, Inserm UMR 1048, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Florian David

    I2MC, Inserm UMR 1048, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Florence Tatin

    I2MC, Inserm UMR 1048, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Edith Renaud-Gabardos

    I2MC, Inserm UMR 1048, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Françoise Pujol

    I2MC, Inserm UMR 1048, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Leila H Diallo

    I2MC, Inserm UMR 1048, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Isabelle Ader

    Stromalab, Inserm U1031, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Laetitia Ligat

    CRCT, Inserm UMR 1037, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Anthony K Henras

    Centre de Biologie Intégrative, Université Paul Sabatier, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  11. Yasufumi Sato

    Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku Universtiy, Sendai, Japan
    Competing interests
    The authors declare that no competing interests exist.
  12. Angelo Parini

    I2MC, Inserm UMR 1048, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  13. Eric Lacazette

    I2MC, Inserm UMR 1048, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  14. Barbara Garmy-Susini

    I2MC, Inserm UMR 1048, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  15. Anne-Catherine Prats

    I2MC, Inserm UMR 1048, Toulouse, France
    For correspondence
    anne-catherine.prats@inserm.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5282-3776

Funding

Region Midi-Pyrenees

  • Anne-Catherine Prats

AFM-Téléthon

  • Edith Renaud-Gabardos
  • Anne-Catherine Prats

Association pour la Recherche sur le Cancer

  • Anne-Catherine Prats

European Commission (REFBIO VEMT)

  • Anne-Catherine Prats

Fondation Toulouse Cancer-Sante

  • Barbara Garmy-Susini

Agence Nationale de la Recherche (ANR-18-CE11-0020-RIBOCARD)

  • Anne-Catherine Prats

Ligue Contre le Cancer

  • Fransky Hantelys
  • Anne-Claire Godet

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

Reviewing Editor

  1. Nahum Sonenberg, McGill University, Canada

Publication history

  1. Received: July 18, 2019
  2. Accepted: December 9, 2019
  3. Accepted Manuscript published: December 9, 2019 (version 1)
  4. Version of Record published: January 7, 2020 (version 2)

Copyright

© 2019, Hantelys 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. Fransky Hantelys
  2. Anne-Claire Godet
  3. Florian David
  4. Florence Tatin
  5. Edith Renaud-Gabardos
  6. Françoise Pujol
  7. Leila H Diallo
  8. Isabelle Ader
  9. Laetitia Ligat
  10. Anthony K Henras
  11. Yasufumi Sato
  12. Angelo Parini
  13. Eric Lacazette
  14. Barbara Garmy-Susini
  15. Anne-Catherine Prats
(2019)
Vasohibin1, a new mouse cardiomyocyte IRES trans-acting factor that regulates translation during early hypoxia
eLife 8:e50094.
https://doi.org/10.7554/eLife.50094

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