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.
-
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.
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
-
- 1,724
- views
-
- 266
- downloads
-
- 18
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
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)
Further reading
-
- Cell Biology
- Developmental Biology
A study in mice reveals key interactions between proteins involved in fibroblast growth factor signaling and how they contribute to distinct stages of eye lens development.
-
- Cell Biology
- Evolutionary Biology
Maintenance of rod-shape in bacterial cells depends on the actin-like protein MreB. Deletion of mreB from Pseudomonas fluorescens SBW25 results in viable spherical cells of variable volume and reduced fitness. Using a combination of time-resolved microscopy and biochemical assay of peptidoglycan synthesis, we show that reduced fitness is a consequence of perturbed cell size homeostasis that arises primarily from differential growth of daughter cells. A 1000-generation selection experiment resulted in rapid restoration of fitness with derived cells retaining spherical shape. Mutations in the peptidoglycan synthesis protein Pbp1A were identified as the main route for evolutionary rescue with genetic reconstructions demonstrating causality. Compensatory pbp1A mutations that targeted transpeptidase activity enhanced homogeneity of cell wall synthesis on lateral surfaces and restored cell size homeostasis. Mechanistic explanations require enhanced understanding of why deletion of mreB causes heterogeneity in cell wall synthesis. We conclude by presenting two testable hypotheses, one of which posits that heterogeneity stems from non-functional cell wall synthesis machinery, while the second posits that the machinery is functional, albeit stalled. Overall, our data provide support for the second hypothesis and draw attention to the importance of balance between transpeptidase and glycosyltransferase functions of peptidoglycan building enzymes for cell shape determination.