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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The translational regulation of ferritin expression currently represents the only well characterized example for eukaryotic translational control by high affinity interactions between a specific cytoplasmic protein, iron regulatory factor [IRF], and an mRNA-binding site, the iron-responsive element [IRE], located in the 5' untranslated region [UTR] of ferritin mRNAs. To elucidate whether IRE/IRF may represent the first physiological example of a more general mechanism for mRNA-specific translational control, high affinity RNA-binding sites for the bacteriophage MS2 coat protein or the spliceosomal protein U1A were introduced into the 5' UTR of capped chloramphenicol acetyltransferase [CAT] transcripts. In the absence of these RNA-binding proteins, CAT mRNA was efficiently translated. Addition of purified MS2 coat protein or U1A caused a specific, dose-dependent repression of CAT biosynthesis in rabbit reticulocyte and wheat germ in vitro translation systems. The translational blockage imposed by the RNA/protein complex was reversible and did not alter the stability of the repressed mRNAs. Translational repression caused by binding of U1A or MS2 proteins to their target mRNAs is shown to be position-dependent in vitro. Thus, mRNA/protein complexes without an a priori role in eukaryotic mRNA translation function as translational effectors with characteristics resembling those of IRE/IRF.
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PMID:Bacteriophage and spliceosomal proteins function as position-dependent cis/trans repressors of mRNA translation in vitro. 145 20

Nitric oxide (NO) produced from L-arginine by NO synthases (NOS) is a transmitter known to be involved in diverse biological processes, including immunomodulation, neurotransmission and blood vessel dilatation. We describe a novel role of NO as a signaling molecule in post-transcriptional gene regulation. We demonstrate that induction of NOS in macrophage and non-macrophage cell lines activates RNA binding by iron regulatory factor (IRFs), the central trans regulator of mRNAs involved in cellular iron metabolism. NO-induced binding of IRF to iron-responsive elements (IRE) specifically represses the translation of transfected IRE-containing indicator mRNAs as well as the biosynthesis of the cellular iron storage protein ferritin. These findings define a new biological function of NO and identify a regulatory connection between the NO/NOS pathway and cellular iron metabolism.
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PMID:Translational regulation via iron-responsive elements by the nitric oxide/NO-synthase pathway. 750 27

Cellular iron metabolism comprises pathways of iron-protein synthesis and degradation, iron uptake via transferrin receptor (TfR) or release to the extracellular space, as well as iron deposition into ferritin and remobilization from such stores. Different cell types, depending on their rate of proliferation and/or specific functions, show strong variations in these pathways and have to control their iron metabolism to cope with individual functions. Studies with cultured cells have revealed a specific cytoplasmic protein, called 'iron regulatory protein' (IRP) (previously known as IRE-BP or IRF), that plays a key role in iron homoeostasis by regulating coordinately the synthesis of TfR, ferritin, and erythroid 5-aminolevulinate synthase (eALAS). Present in all tissues analysed, IRP is identical with the [4Fe-4S] cluster containing cytoplasmic aconitase. Under conditions of iron chelation, IRP is an apo-protein which binds with high affinity to specific RNA stem-loop elements (IREs) located 5' of the initiation codon in ferritin and eALAS mRNA, and 3' in the untranslated region of TfR mRNA. At 5' sites IRF blocks mRNA translation, whereas 3' it inhibits TfR mRNA degradation. Both effects compensate for low intracellular iron concentrations. Under high iron conditions, IRP is converted to the holo-protein and dissociates from mRNA. This reverses the control towards less iron uptake and more iron storage. Iron can therefore be considered as a feedback regulator of its own metabolism. It has recently become evident that nitric oxide, produced by macrophages and other cell types in response to interferon-gamma, induces the IRE-binding activity of IRF. Moreover measurements of the RNA-binding activity of IRP in tissue extracts may provide valuable information on iron availability.
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PMID:Molecular regulation of iron proteins. 788 Nov 53

Transferrin receptor (TfR) expression is regulated by iron at the level of mRNA stability through a factor (IRF/IRE-BP) which binds to specific iron-responsive elements (IRE). On the other hand, growth-dependent regulation of TfR expression is generally believed to be transcriptionally controlled. We analyzed the molecular mechanisms that control TfR gene expression at the onset of cell proliferation in vivo during liver regeneration after partial hepatectomy. The amount of TfR mRNA increased considerably after partial hepatectomy while run-on assays did not show significant changes in TfR gene transcription. RNA band-shift assays documented a significant activation of IRF/IRE-BP specific for the faster migrating IRE-protein complex (IRFB). These changes occurred in the absence of modifications of total liver iron concentration but together with a significant decrease of ferritin content. Moreover, when extreme variations of liver iron content were achieved by either chronic iron overload or severe iron deficiency, liver regeneration was unable to influence IRE-binding activity. We conclude that IRF/IRE-BP-mediated post-transcriptional control can fully account for TfR mRNA induction during liver cell proliferation in vivo. IRF/IRE-BP activation in the absence of changes in total tissue iron content might depend either on a drop of iron levels into the regulatory pool or on a relatively iron-independent mechanism specific for the faster migrating complex.
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PMID:Transferrin receptor gene expression during rat liver regeneration. Evidence for post-transcriptional regulation by iron regulatory factorB, a second iron-responsive element-binding protein. 811 90

The prognostic value of hematological parameters other than hemoglobin (Hb) has been seldom investigated in hemodialysis (HD) patients. We used the predialytic assessment of blood ferritin, blood transferrin, transferrin saturation, blood iron, total iron binding capacity (TIBC), Hb, reticulocyte count, IRF, mean corpuscular volume (MCV), RDW, CHR, in our HD patients, as well as the weekly iron and erythropoietin (EPO) supplementation, to evaluate the relationship with death in the subsequent 12-month period. Data were divided into two groups (group M for dead patients and group V for patients remaining alive after 12 months) and mean +/- SD with significant differences (Student's t-test) were calculated. The following results were obtained: blood transferrin: M (n=21) 1.78 +/- 0.57, V (n=96) 1.72 +/- 0.36 g/L (p=ns); blood iron: M (n=22) 8.66 +/- 5.07, V (n=97) 10.50 +/- 4.57 mmol/L (p=ns); TIBC: M (n=21) 42.69 +/- 13.63, V (n=98) 40.36 +/- 10.33 mmol of iron/L (p=ns); transferrin saturation: M (n=21) 22.10 +/- 13.07, V (n=96) 25.81 +/- 11.79% (p=ns); blood Hb: M (n=22) 107.55 +/-19.70, V (n=98) 111.02 +/- 14.68 g/L (p=ns); MCV: M (n=22) 94.58 +/- 7.35, V (n=98) 93.27 +/- 8.16 fL (p=ns); RDW: M (n=22) 16.60 +/- 1.51, V (n=98) 15.83 +/- 1.39 (p<0.022); soluble transferrin receptors: M (n=18) 1.85 +/- 0.90, V (n=90) 1.89 +/- 0.75 mg/L (p=ns); reticulocyte count: M (n=22) 91.38 +/- 34.69, V (n=98) 87.27 +/- 29.56 *10 9 /L (p=ns); CHR: M (n=22) 31.36 +/- 2.92, V (n=98) 31.46 +/- 3.08 pg (p=ns); IRF: M (n=22) 24.81 +/- 7.55, V (n=98) 23.65 +/- 8.64 (p=ns); intravenous Fe+++ weekly supplementation: M (n=22) 45.45 +/- 26.81, V (n=98) 37.31 +/- 32.25 mg/week (p=ns); a-EPO weekly supple-mentation: M (n=22) 9090.91 +/- 7824.92, V (n=97) 9030.93 +/- 8292.13 UI/week (p=ns). Since it was not feasible to compare an individual event such as death with the spectra of laboratory data or the administered drug amount, the values of each series were in descending order and the number of M patients (approximately 20% of the total) falling into the upper or lower 20% of values was calculated. In front to the expected amount of 4.4 M for each 20%, two M patients fell into the upper 20% and six patients into the lower 20% of blood ferritin values, and, correspondingly, two vs. nine patients for blood iron, four vs. seven patients for transferrin saturation, three vs. seven patients for blood Hb, eight vs. two patients for RDW and six vs. two patients for iron supplementation. Therefore, our patients with a negative prognosis showed an increase in RDW and an iron availability or metabolism disorder.
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PMID:[Hematological and iron parameters to predict mortality in ESRD]. 1578 88