scholarly journals Expression of the two mRNA isoforms of the iron transporter Nrmap2/DMTI in mice and function of the iron responsive element

2002 ◽  
Vol 363 (3) ◽  
pp. 449 ◽  
Author(s):  
Dimitri TCHERNITCHKO ◽  
Monique BOURGEOIS ◽  
Marie-Elise MARTIN ◽  
Carole BEAUMONT
Keyword(s):  
Mrna Isoforms ◽  
Iron Responsive Element ◽  
Iron Transporter ◽  
Responsive Element ◽  
And Function

Expression of the two mRNA isoforms of the iron transporter Nrmap2/DMTI in mice and function of the iron responsive element

2002 ◽  
Vol 363 (3) ◽  
pp. 449-455 ◽  
Author(s):  
Dimitri TCHERNITCHKO ◽  
Monique BOURGEOIS ◽  
Marie-Elise MARTIN ◽  
Carole BEAUMONT
Keyword(s):  
Alternative Splicing ◽  
Iron Deficiency ◽  
Iron Status ◽  
Mrna Isoforms ◽  
Real Time Quantitative Pcr ◽  
Iron Responsive Element ◽  
Mouse Tissues ◽  
Stimulation Of Erythropoiesis ◽  
Responsive Element ◽  
And Function

Nramp2/DMT1 is a transmembrane proton-coupled Fe2+ transporter. Two different mRNAs are generated by alternative splicing; isoform I contains an iron responsive element (IRE), whereas isoform II does not. They encode two proteins differing at their C-terminal end and by their subcellular localization. IRE-mediated stabilization of isoform I mRNA is thought to stimulate DMT1 expression in response to iron deficiency. We have measured the two mRNAs by real-time quantitative PCR in several mouse tissues, in normal conditions or following injection of phenylhydrazine, a potent haemolytic agent. Isoform I mRNA is expressed in the duodenum and is induced by stimulation of erythropoiesis, whereas the non-IRE isoform is mostly induced in erythropoietic spleen. Surprisingly, both isoforms are highly expressed in the kidney and are not regulated by erythropoiesis. To evaluate the role of the IRE in regulating isoform I mRNA stability, in response to variations in cell iron status, several constructs were made in pCDNA3 with either a normal or a mutated IRE placed at the 3′ end of a stable mRNA. These constructs were transfected into HT29 cells and mRNAs were analysed after growing cells in the presence or absence of exogenous iron. There was no difference in the level of expression of the different messages, suggesting that the IRE does not regulate stability of isoform I mRNA. The half-life of the endogenous IRE-mRNA was also measured following actinomycin D addition in iron- or desferrioxamine-treated cells. Decay of the mRNA was very similar in both conditions. These results suggest that additional transcriptional regulations at the promoter level, or iron-dependent regulation of alternative splicing are likely to participate in the induction of isoform I mRNA by iron deficiency.

Structure and Function of the Iron-Responsive Element from Human Ferritin L Chain mRNA

1997 ◽  
Vol 235 (1) ◽  
pp. 212-216 ◽  
Author(s):  
Wolfgang Mikulits ◽  
Thomas Sauer ◽  
Anthony A. Infante ◽  
Jose A. Garcia-Sanz ◽  
Ernst W. Müllner
Keyword(s):  
Structure And Function ◽  
Iron Responsive Element ◽  
Human Ferritin ◽  
Responsive Element ◽  
And Function

scholarly journals Iron-responsive element-binding protein. Phosphorylation by protein kinase C.

1993 ◽  
Vol 268 (36) ◽  
pp. 27363-27370
Author(s):  
R S Eisenstein ◽  
P T Tuazon ◽  
K L Schalinske ◽  
S A Anderson ◽  
J A Traugh
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Phosphorylation ◽  
Binding Protein ◽  
Iron Responsive Element ◽  
Kinase C ◽  
Element Binding Protein ◽  
Responsive Element

scholarly journals Loss of park7 activity has differential effects on expression of iron responsive element (IRE) gene sets in the brain transcriptome in a zebrafish model of Parkinson’s disease

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hui Yung Chin ◽  
Michael Lardelli ◽  
Lyndsey Collins-Praino ◽  
Karissa Barthelson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Function ◽  
Bioinformatic Analysis ◽  
Zebrafish Model ◽  
Iron Responsive Element ◽  
Brain Transcriptome ◽  
Gene Sets ◽  
Oxidative Phosphorylation Pathway ◽  
Responsive Element

AbstractMutation of the gene PARK7 (DJ1) causes monogenic autosomal recessive Parkinson’s disease (PD) in humans. Subsequent alterations of PARK7 protein function lead to mitochondrial dysfunction, a major element in PD pathology. Homozygous mutants for the PARK7-orthologous genes in zebrafish, park7, show changes to gene expression in the oxidative phosphorylation pathway, supporting that disruption of energy production is a key feature of neurodegeneration in PD. Iron is critical for normal mitochondrial function, and we have previously used bioinformatic analysis of IRE-bearing transcripts in brain transcriptomes to find evidence supporting the existence of iron dyshomeostasis in Alzheimer’s disease. Here, we analysed IRE-bearing transcripts in the transcriptome data from homozygous park7−/− mutant zebrafish brains. We found that the set of genes with “high quality” IREs in their 5′ untranslated regions (UTRs, the HQ5′IRE gene set) was significantly altered in these 4-month-old park7−/− brains. However, sets of genes with IREs in their 3′ UTRs appeared unaffected. The effects on HQ5′IRE genes are possibly driven by iron dyshomeostasis and/or oxidative stress, but illuminate the existence of currently unknown mechanisms with differential overall effects on 5′ and 3′ IREs.

An IRP-like protein from Plasmodium falciparum binds to a mammalian iron-responsive element

Blood ◽  
2001 ◽  
Vol 98 (8) ◽  
pp. 2555-2562 ◽  
Author(s):  
Mark Loyevsky ◽  
Timothy LaVaute ◽  
Charles R. Allerson ◽  
Robert Stearman ◽  
Olakunle O. Kassim ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Regulatory Protein ◽  
Protein S ◽  
Fold Increase ◽  
Binding Activity ◽  
Mobility Shift ◽  
Iron Responsive Element ◽  
Element Binding Protein ◽  
Responsive Element ◽  
Electrophoretic Mobility Shift Assays

Abstract This study cloned and sequenced the complementary DNA (cDNA) encoding of a putative malarial iron responsive element-binding protein (PfIRPa) and confirmed its identity to the previously identified iron-regulatory protein (IRP)–like cDNA from Plasmodium falciparum. Sequence alignment showed that the plasmodial sequence has 47% identity with human IRP1. Hemoglobin-free lysates obtained from erythrocyte-stage P falciparum contain a protein that binds a consensus mammalian iron-responsive element (IRE), indicating that a protein(s) with iron-regulatory activity was present in the lysates. IRE-binding activity was found to be iron regulated in the electrophoretic mobility shift assays. Western blot analysis showed a 2-fold increase in the level of PfIRPa in the desferrioxamine-treated cultures versus control or iron-supplemented cells. Malarial IRP was detected by anti-PfIRPa antibody in the IRE-protein complex fromP falciparum lysates. Immunofluorescence studies confirmed the presence of PfIRPa in the infected red blood cells. These findings demonstrate that erythrocyte P falciparum contains an iron-regulated IRP that binds a mammalian consensus IRE sequence, raising the possibility that the malaria parasite expresses transcripts that contain IREs and are iron-dependently regulated.

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