Iron-regulatory element

Finally, we remind our reader that in its apoform, cytoplasmic aconitase is active as an ion regulatory protein (see Chapter 8), binding to iron regulatory elements in the mRNAs of ferritin and transferrin receptor and regulating their translation. 

Theil EC (1994) Iron regulatory elements (IREs) a family of mRNA non-coding sequences. Biochem J 304 1-11... 

Coordinate translational regulation of ferritin mRNA and transferrin receptor mRNA in nonerythroid cells. Iron regulatory proteins (IRP) are RNA-binding proteins that bind to iron regulatory elements (IREs). IREs are hairpin structures with loops consisting of CAGUGN sequences and are located at the 5 -untranslated region (UTR) and 3 -UTR for ferritin mRNA and transferrin mRNA, respectively. 

Aconitase exists as both mitochondrial and cytosolic isoenzyme forms of similar structure. However, the cytosolic isoenzyme has a second function. In its apoenzyme form, which lacks the iron-sulfur cluster, it acts as the much-studied iron regulatory factor, or iron-responsive element binding protein (IRE-BP). This protein binds to a specific stem-loop structure in the messenger RNA for proteins involved in iron transport and storage (Chapter 28).86/9°... 

SELEX has also allowed the characterization of the RNA hairpin, which constitutes the iron responsive element (IRE) recognized by the iron regulatory factor (IRF) protein to post-transcriptionally regulate translatability and decay of mRNAs involved in iron import and storage in eukaryotic cells (Henderson et al., 1994). 

Henderson, B.R., Menotti, E., Bonnard, C. and Kuhn, L.C. (1994) Optimal sequence and structure of iron-responsive elements. Selection of RNA stem-loops with high affinity for iron regulatory factor. J. Biol. Chem., 269, 17481-17489. 

Iron regulatory proteins (IRPs) regulate the cellular iron level in mammalian cells. IRPs are known as cytosol mRNA binding proteins which control the stability or the translation rate of mRNAs of iron metabolism-related proteins such as TfR, ferritin, and 5-aminolevulinic acid synthetase in response to the availability of cellular iron [19-21] after uptake [5]. The regulatory mechanism involves the interaction between the iron-responsive element (IRE) in the 3 or 5 untranslated regions of the transcripts and cytosolic IRPs (IRP-1 and -2). IRP-1 is an iron-sulfur (Fe-S) protein with aconitase activity containing a cubane 4Fe-4S cluster. When Fe is replete, IRP-1 prevails in a 4Fe-4S form as a holo-form and is an active cytoplasmic aconitase. As shown in Fig. 3, when Fe is deplete, it readily loses one Fe from the fourth labile Fe in the Fe-S cluster to become a 3Fe-4S cluster and in this state has little enzymatic activity [22, 23]. 

Thomson AM, Rogers IT, Leedman PJ. Iron-regulatory proteins, iron-responsive elements and ferritin mRNA translation. Int. J. Biochem. Cell. Biol. 1999 31 1139-1152. 

A family of proteins with common ligand-binding domains Section 31.1.4 Independent evolution of DNA-binding sites of regulatory proteins Section 311.5 CpG islands Section 31.2.5 Iron response elements Section 31.4.2... 

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