Transport, Storage, and Homeostasis of Metal Ions - Biological Inorganic Chemistry - page 172

cytosolic iron sensors. In conditions of iron deficiency, IRPs bind with high-affinity (K D w 100 pM) to stem

loops, known as iron regulatory elements (IREs), in mRNAs encoding the regulated proteins ( Fig. 8.18 ) . When the

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(a)

(b)

FIGURE 8.18 Outline of translational regulation of mRNAs of a number of proteins involved in iron metabolism in low and high iron
(a) Ferritin mRNA (b) TfR mRNA. IRPs bind to IREs located in either the 5 0 -or3 0 -UTRs of specific mRNAs. During low iron conditions, IRP1
and IRP2 bind with high affinity to 5 0 IREs and to the five 3 0 IREs in TfR mRNA, resulting in the translational repression of 5 0 IRE-containing
mRNAs and the stabilisation of the Tf R mRNA. During high iron conditions, IRPs lose their affinity for IREs, increasing translation of 5 0 IRE-
containing mRNAs and mediating degradation of the TfR mRNA. Increased iron levels result in the conversion of the IRP1 RNA binding form
into the [4Fe 4S] cluster c-acon form, while increased iron and/or haem levels mediate IRP2 proteasomal degradation. (From Crichton, 2009 .

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IREs are in the 5 0 -untranslated region of the mRNA, as is the case for ferritin and ferroportin, binding of IRPs
prevents initiation of translation. In contrast, in the case of the transferrin receptor and DMT1, where the IREs are