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https://hdl.handle.net/2440/9694
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Type: | Journal article |
Title: | Hypoxia-inducible factor-1a mRNA contains an internal ribosome entry site that allows efficient translation during normoxia and hypoxia |
Author: | Lang, K. Kappel, A. Goodall, G. |
Citation: | Molecular Biology of the Cell, 2002; 13(5):1792-1801 |
Publisher: | Amer Soc Cell Biology |
Issue Date: | 2002 |
ISSN: | 1059-1524 1939-4586 |
Editor: | Wickens, M.P. |
Statement of Responsibility: | 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 |
DOI: | 10.1091/mbc.02-02-0017 |
Published version: | http://dx.doi.org/10.1091/mbc.02-02-0017 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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