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.
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Data from: Vasohibin1, a new IRES trans-acting factor for induction of (lymph)angiogenic factors in early hypoxiaDryad Digital Repository, doi:10.5061/dryad.2330r1b.
Article and author information
Author details
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
- Nahum Sonenberg, McGill University, Canada
Version history
- Received: July 18, 2019
- Accepted: December 9, 2019
- Accepted Manuscript published: December 9, 2019 (version 1)
- 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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