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

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dc.contributor.authorLang, K.
dc.contributor.authorKappel, A.
dc.contributor.authorGoodall, G.
dc.contributor.editorWickens, M.P.
dc.date.issued2002
dc.descriptionCopyright © 2002 by The American Society for Cell Biology
dc.description.abstractHIF-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.
dc.description.statementofresponsibilityKenneth J. D. Lang, Andreas Kappel, and Gregory J. Goodall
dc.identifier.citationMolecular Biology of the Cell, 2002; 13(5):1792-1801
dc.identifier.doi10.1091/mbc.02-02-0017
dc.identifier.issn1059-1524
dc.identifier.issn1939-4586
dc.identifier.orcidGoodall, G. [0000-0003-1294-0692]
dc.identifier.urihttp://hdl.handle.net/2440/9694
dc.language.isoen
dc.publisherAmer Soc Cell Biology
dc.source.urihttps://doi.org/10.1091/mbc.02-02-0017
dc.subjectHela Cells
dc.subject3T3 Cells
dc.subjectRibosomes
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectOxygen
dc.subjectIntercellular Signaling Peptides and Proteins
dc.subjectVascular Endothelial Growth Factors
dc.subjectVascular Endothelial Growth Factor A
dc.subjectEndothelial Growth Factors
dc.subjectTranscription Factors
dc.subjectRNA, Messenger
dc.subject5' Untranslated Regions
dc.subjectLymphokines
dc.subjectCulture Media, Serum-Free
dc.subjectProtein Biosynthesis
dc.subjectGenes, myc
dc.subjectHypoxia-Inducible Factor 1, alpha Subunit
dc.subjectHypoxia
dc.titleHypoxia-inducible factor-1a mRNA contains an internal ribosome entry site that allows efficient translation during normoxia and hypoxia
dc.typeJournal article
pubs.publication-statusPublished

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