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Hypoxia-inducible Factor-1α mRNA Contains an Internal Ribosome Entry Site That Allows Efficient Translation during Normoxia and Hypoxia

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Lang, Kenneth J. D., Kappel, Andreas, Goodall, Gregory J.·2002·Molecular Biology of the Cell

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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.

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Authors: Lang, K. J. D., Kappel, A., & Goodall, G. J.
Affiliations: South Australia Pathology (AU)
Max Planck Society (DE)
ORCID: Goodall, Gregory J.
Venue: Molecular Biology of the Cell
Publisher: American Society for Cell Biology (ASCB)
Published: 2002-05
Volume: 13
Issue: 5
Pages: 1792-1801
ISSN: 1059-1524 (ISSN-L)
1939-4586
DOI: 10.1091/mbc.02-02-0017
PMC: PMC111144
OpenAlex: W2146299409
Cited by: 314
References: 36
Citations by year: 2026: 5 · 2025: 6 · 2024: 8 · 2023: 4 · 2022: 6 · 2021: 11 · 2020: 12 · 2019: 8 · 2018: 8 · 2017: 7 · 2016: 14 · 2015: 13 · 2014: 19 · 2013: 11 · 2012: 22
FWCI: 5.58
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Molecular Biology of the Cell (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
Funders: National Heart Foundation of Australia
Royal Adelaide Hospital
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords: hypoxia-inducible factor-1α, internal ribosome entry site, 5' untranslated region, mRNA translation, hypoxia, cap-dependent translation, serum deprivation, polysome profiling, NIH3T3 cells
MeSH terms: Animals, Hypoxia, HeLa Cells, Humans, Lymphokines, Oxygen, Ribosomes, RNA, Messenger, Transcription Factors, Protein Biosynthesis, Endothelial Growth Factors, Genes, myc, 3T3 Cells, Culture Media, Serum-Free, 5' Untranslated Regions, Intercellular Signaling Peptides and Proteins, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Mice, Hypoxia-Inducible Factor 1, alpha Subunit

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Hypoxia-inducible Factor-1α mRNA Contains an Internal Ribosome Entry Site That Allows Efficient Translation during Normoxia and Hypoxia

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