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

Prats, Anne-Catherine, Délégation Midi-Pyrénées, Limousin, https://orcid.org/0000-0002-5282-3776

Hantelys, Fransky, University of Toulouse

Godet, Anne-Claire, University of Toulouse

David, Florian, University of Toulouse

Tatin, Florence, University of Toulouse

Renaud-Gabardos, Edith, University of Toulouse

Pujol, Françoise, University of Toulouse

Diallo, Leila H., University of Toulouse

Ader, Isabelle, Centre Occitanie-Toulouse

Ligat, Laetitia, University of Toulouse

Henras, Anthony K., University of Toulouse

Sato, Yasufumi, Pennsylvania Department of Aging

Parini, Angelo, University of Toulouse

Lacazette, Eric, University of Toulouse

Garmy-Susini, Barbara, University of Toulouse

anne-catherine.prats@inserm.fr

Published Aug 24, 2020 on Dryad. https://doi.org/10.5061/dryad.nvx0k6dq7

Cite this dataset

Prats, Anne-Catherine et al. (2020). Vasohibin1, a new mouse cardiomyocyte IRES trans-acting factor that regulates translation in early hypoxia [Dataset]. Dryad. https://doi.org/10.5061/dryad.nvx0k6dq7

Abstract

Hypoxia, a major inducer of angiogenesis, triggers major changes in gene expression at the transcriptional level. Furthermore, under hypoxia, 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) that is able to bind RNA and to activate the FGF1 IRES in hypoxia, but which tends to inhibit several IRESs in normoxia. VASH1 depletion has 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 triggering new vessel formation in ischemic heart.

Methods

The sequences of the different lentivector plasmids are provided.

Funding

French Muscular Dystrophy Association

Fondation ARC pour la Recherche sur le Cancer

European Commission, Award: REFBIO VEMT

Agence Nationale de la Recherche, Award: ANR-18-CE11-0020-RIBOCARD

La Ligue Contre le Cancer

Region Midi-Pyrenees

University Cancer Institute Toulouse Oncopole