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|Title:||Hypoxia-inducible factor-1a mRNA contains an internal ribosome entry site that allows efficient translation during normoxia and hypoxia|
|Citation:||Molecular Biology of the Cell, 2002; 13(5):1792-1801|
|Publisher:||Amer Soc Cell Biology|
|Kenneth J. D. Lang, Andreas Kappel, and Gregory J. Goodall|
|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 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.|
|Keywords:||Hela Cells; 3T3 Cells; Ribosomes; Animals; Humans; Mice; Oxygen; Intercellular Signaling Peptides and Proteins; Vascular Endothelial Growth Factors; Vascular Endothelial Growth Factor A; Endothelial Growth Factors; Transcription Factors; RNA, Messenger; 5' Untranslated Regions; Lymphokines; Culture Media, Serum-Free; Protein Biosynthesis; Genes, myc; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia|
|Description:||Copyright © 2002 by The American Society for Cell Biology|
|Appears in Collections:||Medicine publications|
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