Vasohibin1, a new IRES trans-acting factor for induction of (lymph)angiogenic factors in early hypoxia

Fransky Hantelys, Anne Claire Godet, Florian David, Florence Tatin, Edith Renaud-Gabardos, Françoise Pujol, Leila Diallo, Isabelle Ader, Laetitia Ligat, Anthony K. Henras, Yasufumi Sato, Angelo Parini, Eric Lacazette, Barbara Garmy-Susini, Anne Catherine Prats

Research output: Contribution to journalArticlepeer-review

Abstract

Hypoxia, a major inducer of angiogenesis, is known to trigger 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 cardiomyocytes: most genes are not induced at the transcriptome-, but at the translatome level, including all IRES-containing mRNAs. Our data reveal activation of (lymph)angiogenic mRNA IRESs in early hypoxia. We identify vasohibin1 (VASH1) as an IRES trans-acting factor (ITAF) able to activate FGF1 and VEGFD IRESs in hypoxia while it inhibits several IRESs in normoxia. Thus this new ITAF may have opposite effects on IRES activities. These data suggest a generalized process of IRES-dependent translational induction of (lymph)angiogenic growth factors expression in early hypoxia, whose pathophysiological relevance is to trigger formation of new functional vessels in ischemic heart. VASH1 is not always required, indicating that the IRESome composition is variable, thus allowing subgroups of IRESs to be activated under the control of different ITAFs.

Original languageEnglish
JournalUnknown Journal
DOIs
Publication statusPublished - 2018 Feb 5

Keywords

  • cardiomyocyte
  • hypoxia
  • IRES
  • translational control
  • vasohibin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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