Role of RNA secondary structure of the iron-responsive element in translational regulation of ferritin synthesis.
Iron regulates synthesis of the iron storage protein ferritin at the translational level through interaction between a stem-loop structure, the iron-responsive element (IRE), located in the 5'-untranslated region (5'-UTR) of ferritin mRNAs, and a protein, the iron regulatory protein (IRP). The role of IRE secondary structure in translational regulation of ferritin synthesis was explored by introducing ferritin constructs containing mutations in the IRE into Rat-2 fibroblasts. Our in vivo studies demonstrate that size and sequence of the loop within the IRE and the distance and/or spatial relationship of this loop to the bulged nucleotide region closest to the loop must be preserved in order to observe iron-dependent translation of ferritin mRNA. In contrast, changes in nucleotide sequence of the upper stem can be introduced without affecting translational regulation in vivo, as long as a stem can be formed. Our in vivo results suggest that only a very small variation in the affinity of interaction of IRP with IRE can be tolerated in order to maintain iron-dependent regulation of translation.
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D005293:Ferritins / Q000096:biosynthesis* / Q000235:genetics; D005347:Fibroblasts; D017930:Genes, Reporter / Q000235:genetics; D006418:Heme / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics; D051381:Rats
D002614:Chelating Agents; D012333:RNA, Messenger; D006418:Heme; D005293:Ferritins; D007501:Iron; D003676:Deferoxamine