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12 Translational Control of Ferritin

Tracey A. Rouault, Richard D. Klausner, Joe B. Harford


The translation of messenger RNAs encoding ferritin is highly regulated by iron. A single copy of an RNA motif known as an iron-responsive element or IRE (see Fig. 1) is found within the 5′-untranslated region (5′ UTR) of the mRNAs that encode all known vertebrate ferritins. The control of translation of ferritin mRNA by iron is mediated by regulation of an interaction between the IRE and a cytosolic protein. This protein, which binds to the IRE with high affinity and specificity when cells are iron-depleted, has been called the IRE-binding protein (IRE-BP) (Leibold and Munro 1988; Rouault et al. 1988), iron regulatory factor (IRF) (Müllner et al. 1989), ferritin repressor protein (FRP) (Walden et al. 1989), and P90 (Harrell et al. 1991). Recently, a consensus has emerged that favors the term iron regulatory protein (IRP), and we adhere to this convention here. There are now two relatively well-characterized iron regulatory proteins that are described in this chapter. The protein originally called IRE-BP is henceforth referred to as IRP1, and a second IRP that is less abundant in the majority of tissues tested is referred to as IRP2.

In addition to the role of the IRE in mediating the regulation of ferritin biosynthesis, an IRE that functions to produce IRP1-mediated translational regulation is present in the 5′ UTR of the mRNA for the erythroid form of δ-aminolevulinic acid (ALA) synthase, the rate-limiting step in the heme biosynthetic pathway (Dierks 1990; Cox et al. 1991; Dandekar et al. 1991; Bhasker et al....

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