Efficient translation of mouse hypoxia-inducible factor-1alpha under normoxic and hypoxic conditions

Biochim Biophys Acta. 2000 Sep 7;1493(1-2):125-34. doi: 10.1016/s0167-4781(00)00172-x.


The heterodimeric hypoxia-inducible factor-1 (HIF-1), consisting of the subunits HIF-1alpha and HIF-1beta/ARNT, is a master transcriptional regulator of oxygen homeostasis. Under hypoxic conditions, HIF-1alpha levels very rapidly increase, mostly due to protein stabilization. However, translational regulation of HIF-1alpha has not been directly analyzed so far. Mouse HIF-1alpha exists as two mRNA isoforms (termed mHIF-1alphaI.1 and mHIF-1alphaI. 2) containing structurally different 5'-termini which might modulate translation initiation. Whereas the in vitro translation efficiency of these two mRNA isoforms was about equal, the mHIF-1alphaI.2 5'-untranslated region (5'-UTR) conferred significantly higher in vivo luciferase reporter gene activity than the mHIF-1alphaI.1 5'-UTR. Similar corresponding luciferase mRNA levels indicate translational rather than transcriptional alterations. Reporter gene expression was not affected upon exposure of transiently transfected cells to hypoxia (1% oxygen). Direct assessment of translational regulation by polysomal profile analysis of HeLaS3 cells showed that HIF-1alpha (and to a lower extent ARNT) mRNA was found mainly in the translationally active polyribosomal fractions under both normoxic and hypoxic conditions. In contrast, the association of mRNAs for beta-actin and ribosomal protein L28 with the polyribosomal fractions was substantially reduced under hypoxic conditions, suggesting decreased overall protein synthesis. Thus, efficient translation of mouse HIF-1alpha in a situation where the general translation efficiency is reduced represents a prerequisite for the very rapid accumulation of HIF-1alpha protein upon exposure to hypoxia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aryl Hydrocarbon Receptor Nuclear Translocator
  • Cell Hypoxia
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • Dimerization
  • Exons
  • Gene Expression Regulation
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Mice
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • Plasmids
  • Protein Biosynthesis
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / genetics
  • RNA, Messenger / biosynthesis
  • Receptors, Aryl Hydrocarbon*
  • Transcription Factors / genetics
  • Transfection


  • ARNT protein, human
  • Arnt protein, mouse
  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • Protein Isoforms
  • RNA, Messenger
  • Receptors, Aryl Hydrocarbon
  • Transcription Factors
  • Aryl Hydrocarbon Receptor Nuclear Translocator