Hypoxia-inducible Factor-1α mRNA Contains an Internal Ribosome Entry Site That Allows Efficient Translation during Normoxia and Hypoxia
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 stabilized in hypoxic cells. Using polysome profile a...
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Published in | Molecular biology of the cell Vol. 13; no. 5; pp. 1792 - 1801 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
The American Society for Cell Biology
01.05.2002
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Online Access | Get full text |
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Summary: | 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 stabilized in hypoxic cells. Using polysome profile analysis, we found that translation of HIF-1α 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-1α mRNA contains an internal ribosome entry site (IRES), we constructed a dicistronic reporter with the HIF-1α 5′UTR inserted between two reporter coding regions. We found that the HIF-1α 5′UTR promoted translation of the downstream reporter, indicating the presence of an IRES. The IRES had activity comparable to that of the well-characterized 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-1α 5′UTR allows translation to be maintained under conditions that are inhibitory to cap-dependent translation. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 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@imvs.sa.gov.au. |
ISSN: | 1059-1524 1939-4586 |
DOI: | 10.1091/mbc.02-02-0017 |