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A more recent version of this article appeared on May 1, 2002
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Submitted on August 27, 2001
Revised on January 25, 2002
Accepted on February 11, 2002
mRNA Contains an Internal Ribosome Entry Site that allows efficient translation during normoxia and hypoxia
1 Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Frome Road, Adelaide, South Australia 5000, Australia
2 Max-Planck-Institut für physiologische und klinische Forschung, W.G. Kerckhoff Institut, Abteilung Molekulare Zellbiologie, 61231 Bad Nauheim, Germany (present address: Aventis Research and Technologies GmbH and Co KG Operative Forschung, Industriepark Hoechst, Gebäude G 830, D-65926 Frankfurt am Main, Germany)
* Corresponding author. E-mail address: greg.goodall{at}imvs.sa.gov.au.
HIF-1 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-1 protein is rapidly degraded in cells supplied with adequate oxygen, but is stabilised in hypoxic cells. Using polysome profile analysis we found that translation of HIF-1 mRNA in NIH3T3 cells is spared the general reduction in translation rate that occurs during hypoxia. To assess whether the 5'UTR of the HIF-1 mRNA contains an internal ribosome entry site (IRES) we constructed a dicistronic reporter with the HIF-1 5'UTR inserted between two reporter coding regions. We found that the HIF-1 5'UTR promoted translation of the downstream reporter, indicating the presence of an IRES. The IRES had comparable activity to that of the well characterised c-myc IRES. IRES activity was not affected by hypoxic conditions that caused a reduction in cap-dependent translation and IRES activity was less affected by serum-starvation than was cap-dependent translation. These data indicate that the presence of an IRES in the HIF-1 5'UTR allows translation to be maintained under conditions that are inhibitory to cap-dependent translation.
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