A model for the structure and functions of iron-responsive elements ☆

Abstract Most eukaryotic cells express two proteins, whose biosynthetic rates are determined by the intracellular iron status. The genes for both these proteins, ferritin and the transferrin receptor (TfR), are regulated at the post-transcriptional level, but by entirely different mechanisms. Ferritin mRNA levels are not affected by acute changes in iron availability. Ferritin biosynthesis is regulated translationally via a defined element contained within the 5' untranslated region (UTR) of the ferritin mRNA. This element has been highly conserved during evolution and has been termed an iron-responsive element (IRE). In contrast to ferritin, the regulation of TfR biosynthesis is mirrored by equivalent changes in TfR mRNA levels. The genetic information for this regulation is mostly located in the region of the gene encoding the 3' UTR of the TfR mRNA. Five elements that closely resemble the ferritin IRE are contained within the region which is critical for TfR regulation. The IRE is suggested to function by forming a specific stem-loop structure that interacts with a transacting factor in an iron-dependent fashion. We present a model that accommodates the mediation of distinct post-transcriptional regulatory phenomena via IREs.