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

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.