Iron responsive regulator

Protoporphyrin is a fluorescent compound whereas heme is not, and therefore we screened a population of Tn5-induced mutants that formed fluorescent colonies imder ultraviolet light. The resultant mutant, strain LODTM5, had the desired phenotype in that it accumulated protoporphyrin only under iron limitation, it was not defective in the last two steps of the heme pathway, and it was not a heme auxotroph. Strain LODTM5 carries a loss-of-function mutation in a new gene named irr (iron responsive regulator) that encodes a protein predicted to contain a helix-tum-helix motif of the GntR family of bacterial transcriptional regulators. 

Recent studies have further examined the iron stress response of pseudomonads using an iron-regulated, ice-nucleation gene reporter (inaZ) for induction of the iron stress response (17,18,84). This particular reporter system was developed by Loper and Lindow (85) for study of microbial iron stress on plant surfaces but was later employed in soil assays. In initial. studies, cells of Pseudomonas fluorescens and P. syringae that contained the pvd-inaZ fusion were shown to express iron-responsive ice-nucleation activity in the bean rhizosphere and phyllosphere. Addition of iron to leaves or soil reduced the apparent transcription of the pvd-inaZ reporter gene, as shown by a reduction in the number of ice nuclei produced. 

Fur has a regulatory influence on the acid-shock response in E. coli and Salmonella. The acid-response reactions are important for the cells to survive when they pass the acidic gut. In Salmonella, a Fur-dependent, but iron-independent, regulation of acid-response genes is observed. Certain point mutations of Fur (e.g. H90R) do not respond to iron, but are able to regulate an acid-response gene (Foster, 2000). Unfortunately, the functions of the Fur-dependent gene products in acid response are not known. 

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). 

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]. 

Hail DJ, Rouaoult TA, Harford JB, Kennedy MC, Bondin GA, Beinert H, Klausner RD (1992) Cellular regulation of the iron-responsive element binding protein disassembly of the cubane iron-sulfur cluster results in high-affinity RNA binding. Proc Natl Acad Sci USA 89 11735-11739... 

Guo B, Yu Y, Leibold EA (1994) Iron regulates cytoplasmic levels of a novel iron-responsive element-binding protein without aconitase activity. J Biol Chem 269 24252-24260... 

In eukaryotes, genes encoding proteins that transport and store iron are regulated at the translational level. Iron-response elements, structures that are present in certain mRNAs, are bound by an IRE-binding protein when this protein is not binding iron. Whether the expression of a gene is stimulated or inhibited in response to changes in the iron status of a cell depends on the location of the IRE within the mRNA. 

Regulation of Irori Requiiing Enzymes and the Iron Response Element... 

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