Hypoxia-inducible factor-1α mRNA contains an internal ribosome entry site that allows efficient translation during normoxia and hypoxia

Abstract

HIF-1α is the regulated subunit of the HIF-1 transcription factor, which induces transcription of a number of genes involved in the cellular response to hypoxia. The HIF-1α protein is rapidly degraded in cells supplied with adequate oxygen, but is stabilised in hypoxic cells. Using polysome profile analysis, it was found that translation of HIF-1α mRNA in NIH3T3 cells is spared the general reduction in translation rate that occurs during hypoxia. Further investigation found that the HIF-1α 5'UTR promoted translation of the downstream reporter, indicating the presence of an internal ribosome entry site (IRES). Indications are that the presence of the IRES in the HIF-1α 5'UTR is to allow translation to be maintained under conditions that are inhibitory to cap-dependent translation.