Coordinate post-transcriptional regulation of ferritin and transferrin receptor expression: the role of regulated RNA-protein interaction.
Excess iron results in an increase in the translation of ferritin mRNA and a decrease in the stability of transferrin receptor (TfR) mRNA. These coordinate regulatory events are mediated by similar sequence/structure motifs that exist within the 5' untranslated region (5'UTR) of the ferritin mRNA and the 3'UTR of the TfR mRNA. We have referred to these motifs as iron-responsive elements (IREs). The IREs from both transcripts interact with a cytoplasmic protein that we have called the IRE-binding protein (IRE-BP). The activity but not the amount of the IRE-BP is dependent on the cellular iron status. The biochemical basis for the altered activity of the IRE-BP appears to be the reversible oxidation-reduction of one or more cysteines in the IRE-BP. The IRE-BP is a 90- to 95-kD cytosolic protein that has been purified to homogeneity by RNA affinity chromatography, and the cDNA corresponding to the IRE-BP has been molecularly cloned. Collectively, our data support a model in which the interaction between the IRE-BP and the ferritin IRE results in attenuation of translation, and similar interaction with TfR mRNA can protect the transcript from rapid degradation mediated by a rapid turnover determinant within the 3'UTR.
Harford
J B
JB
Cell Biology and Metabolism Branch, National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, Md.
Klausner
R D
RD
D001483:Base Sequence; D005293:Ferritins / Q000235:genetics*; D007501:Iron / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D011990:Receptors, Transferrin / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid
D012333:RNA, Messenger; D011990:Receptors, Transferrin; D005293:Ferritins; D007501:Iron