Vasohibin1, a new mouse cardiomyocyte ires trans-acting factor that regulates translation 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

12 Citations (Scopus)

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.

Original languageEnglish
Article numbere50094
JournaleLife
Volume8
DOIs
Publication statusPublished - 2019 Dec

Keywords

  • Cardiomyocyte
  • Hypoxia
  • IRES
  • Translational control
  • Vasohibin

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