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r1={au,ua,gc,cg,gu,ug}
(p1=2...8 c p2=5...5 CAGWGH r1~p2 r1~p1 | 
p3=2...8 nnc p4=5...5 CAGWGH r1~p4 n r1~p3 |
p5=6...8 c p6=2...2 p7=3...3 CAGWGH r1~p7 u r1~p6 r1~p5 )

The "iron-responsive element" (IRE) is a particular hairpin structure located in the 5'-untranslated region (5'-UTR) or in the 3'-untranslated region (3'-UTR) of various mRNAs coding for proteins involved in cellular iron metabolism. The IREs are recognized by trans-acting proteins known as Iron Regulatory Proteins (IRPs) that control mRNA translation rate and stability. Two closely related IRPs, denoted as IRP-1 and IRP-2, have been identified so far which bind IREs and become inactivated (IRP-1) or degradated (IRP-2) when the iron level in the cell increases. IRPs show a significant degree of similarity to mitochondrial aconitase (EC 4.2.1.3). It has been shown that under high iron conditions IRP-1, which contains a 4Fe-4S cluster that possibly acts as a cellular iron biosensor, has enzymatic activity and may act as a cytosolic aconitase. Cellular iron homeostasis in mammalian cells is maintained by the coordinate regulation of the expression of "Transferrin receptor", which determines the amount of iron acquired by the cell, and of "Ferritin", an iron storage protein, which determines the degree of intracellular iron sequestration. Thus if the cell requires more iron, the level of transferrin receptor has to increase and conversely the level of ferritin has to decrease. Ferritin, in vertebrates, consists of 24 protein subunits of two types, type H with Mr of 21 kDa and type L with Mr of 19-20 kDa. The apoprotein (Mr 450 kDa) is able to store up to 4500 Fe (III) atoms. The 5'-UTR of H- and L ferritin mRNAs contain one IRE whereas multiple IREs are located in the 3'-UTR of transferrin receptor mRNA. In the case of low iron concentration, IRPs are able to bind the IREs in the 5'-UTR of H- and L-Ferritin mRNAs repressing their translation and the IREs in the 3'-UTR of transferrin mRNA increasing its stability. Conversely, if iron concentration is high, IRP binding is diminished, which increases translation of ferritins and downregulate expression of the transferrin receptor. IREs have also been found in the 5' and 3'UTRs of mRNAs encoding other proteins involved in iron metabolism such as divalent metal transporter 1 (DMT1-, DCT1-, NRAMP2-, SLC11A2), erythroid 5-aminolevulinic-acid synthase (eALAS) , cell division cycle 14A (CDC14A), mitochondrial aconitase, Drosophila succinate dehydrogenase, and iron regulated transporters (FPN1-, IREG1-, MTP1-, SLC40A1). Two major alternative IRE consensus have been found. In certain IREs the bulge is best drawn with a single unpaired cytosine, whereas in others the cytosine nucleotide and two additional bases seem to oppose one free 3' nucleotide. Some evidences also suggest a structured loop with an interaction between nucleotide C1 and G5. The lower stem can be of variable length and is AU-rich in transferrin mRNA (see Figure, W=A,U and D=not G).

To be noted that a variant IRE structure has been identified in specific alternative splicing mRNA isoforms of the SLC11A2 gene.