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

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.

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.

Metrics

  • 266
    downloads

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Share this article

https://doi.org/10.7554/eLife.50094

Further reading

    1. Cancer Biology
    2. Cell Biology
    Zuzana Outla, Gizem Oyman-Eyrilmez ... Martin Gregor
    Research Article

    The most common primary malignancy of the liver, hepatocellular carcinoma (HCC), is a heterogeneous tumor entity with high metastatic potential and complex pathophysiology. Increasing evidence suggests that tissue mechanics plays a critical role in tumor onset and progression. Here, we show that plectin, a major cytoskeletal crosslinker protein, plays a crucial role in mechanical homeostasis and mechanosensitive oncogenic signaling that drives hepatocarcinogenesis. Our expression analyses revealed elevated plectin levels in liver tumors, which correlated with poor prognosis for HCC patients. Using autochthonous and orthotopic mouse models we demonstrated that genetic and pharmacological inactivation of plectin potently suppressed the initiation and growth of HCC. Moreover, plectin targeting potently inhibited the invasion potential of human HCC cells and reduced their metastatic outgrowth in the lung. Proteomic and phosphoproteomic profiling linked plectin-dependent disruption of cytoskeletal networks to attenuation of oncogenic FAK, MAPK/Erk, and PI3K/Akt signatures. Importantly, by combining cell line-based and murine HCC models, we show that plectin inhibitor plecstatin-1 (PST) is well-tolerated and potently inhibits HCC progression. In conclusion, our study demonstrates that plectin-controlled cytoarchitecture is a key determinant of HCC development and suggests that pharmacologically induced disruption of mechanical homeostasis may represent a new therapeutic strategy for HCC treatment.

    1. Cell Biology
    2. Plant Biology
    Baihong Zhang, Shuqin Huang ... Wenli Chen
    Research Article

    Autophagy-related gene 6 (ATG6) plays a crucial role in plant immunity. Nonexpressor of pathogenesis-related genes 1 (NPR1) acts as a signaling hub of plant immunity. However, the relationship between ATG6 and NPR1 is unclear. Here, we find that ATG6 directly interacts with NPR1. ATG6 overexpression significantly increased nuclear accumulation of NPR1. Furthermore, we demonstrate that ATG6 increases NPR1 protein levels and improves its stability. Interestingly, ATG6 promotes the formation of SINCs (SA-induced NPR1 condensates)-like condensates. Additionally, ATG6 and NPR1 synergistically promote the expression of pathogenesis-related genes. Further results showed that silencing ATG6 in NPR1-GFP exacerbates Pst DC3000/avrRps4 infection, while double overexpression of ATG6 and NPR1 synergistically inhibits Pst DC3000/avrRps4 infection. In summary, our findings unveil an interplay of NPR1 with ATG6 and elucidate important molecular mechanisms for enhancing plant immunity.