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

Elife. 2019 Dec 9:8:e50094. doi: 10.7554/eLife.50094.

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.

Keywords: IRES; angiogenesis; cardiomyocyte; cell biology; chromosomes; gene expression; hypoxia; mouse; translational control; vasohibin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Humans
  • Hypoxia / metabolism*
  • Internal Ribosome Entry Sites / physiology*
  • Mice
  • Myocytes, Cardiac / metabolism*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • RNA, Messenger / metabolism
  • RNA-Binding Motifs
  • Trans-Activators / metabolism*
  • Transcriptome

Substances

  • Cell Cycle Proteins
  • Internal Ribosome Entry Sites
  • RNA, Messenger
  • Trans-Activators
  • VASH1 protein, human
  • Vash1 protein, mouse

Associated data

  • Dryad/10.5061/dryad.2330r1b