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

Abstract:

:HIF-1alpha 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-1alpha 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-1alpha 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-1alpha mRNA contains an internal ribosome entry site (IRES), we constructed a dicistronic reporter with the HIF-1alpha 5'UTR inserted between two reporter coding regions. We found that the HIF-1alpha 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-1alpha 5'UTR allows translation to be maintained under conditions that are inhibitory to cap-dependent translation.

journal_name

Mol Biol Cell

authors

Lang KJ,Kappel A,Goodall GJ

doi

10.1091/mbc.02-02-0017

keywords:

subject

Has Abstract

pub_date

2002-05-01 00:00:00

pages

1792-801

issue

5

eissn

1059-1524

issn

1939-4586

journal_volume

13

pub_type

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