Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The level of mRNA encoding the transferrin receptor (TfR) is regulated by iron, and this regulation is mediated by a portion of the 3' untranslated region (UTR) of the TfR transcript. This portion of 3' UTR of the human TfR mRNA contains five RNA elements that have structural similarity to the iron-responsive element (IRE) found as a single copy in the 5' UTR of the mRNA for ferritin, whose translation is regulated by iron. Moreover, five very similar elements are also contained in the 3' UTR of the chicken TfR mRNA. Cytosolic extracts of human cell lines are shown by a gel shift assay involving RNase T1 protection to contain an IRE-binding protein capable of specific interaction with the human TfR 3' UTR. When the protecting protein is removed, the protected RNA can be digested with RNase T1 to yield oligoribonucleotide fragments characteristic of two of the IREs contained in the TfR 3' UTR. As judged by cross-competition experiments, the same IRE-binding protein interacts with the ferritin IRE. The apparent affinity of RNA sequence elements for the IRE-binding protein is shown to depend upon the sequence of the RNA. A comprehensive secondary structure for the regulatory region of the TfR mRNA is proposed based on the experimentally demonstrated presence of at least two IRE-like structural elements.
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PMID:A cytosolic protein binds to structural elements within the iron regulatory region of the transferrin receptor mRNA. 249 73

We have previously demonstrated that phorbol myristate acetate (PMA) up-regulates H-ferritin gene expression in myeloid cells by stabilization of its message. In the present report, we showed that insertion of the 3'-untranslated region (3'-UTR) of H-ferritin mRNA at the 3'-end of luciferase coding sequence significantly reduced the stability of luciferase mRNA in human monocytic THP-1 cells. However, the half-life of the chimeric transcript was markedly prolonged after PMA treatment. A cytosolic protein factor from THP-1 cells was found to specifically bind to H-ferritin 3'-UTR. PMA treatment of THP-1 cells resulted in the reduction of the RNA binding activity in a time-dependent manner. Deletion analysis and RNase T1 mapping revealed a pyrimidine-rich sequence within the 3'-UTR which interacts with the protein factor. Competition experiments with homoribopolymers further demonstrated the importance of uridines for the binding activity. Point mutations in uridines of the pyrimidine-rich sequence reduced the protein binding to 3'-UTR, while increasing the stability of the chimeric luciferase transcript. Together, these results demonstrate that the pyrimidine-rich sequence in the 3'-UTR is involved in post-transcriptional regulation of H-ferritin gene expression in myeloid cells.
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PMID:Post-transcriptional regulation of H-ferritin mRNA. Identification of a pyrimidine-rich sequence in the 3'-untranslated region associated with message stability in human monocytic THP-1 cells. 1051 12

We have investigated the analysis of RNA by use of terminal transferase-dependent PCR (TDPCR), a procedure previously used for the analysis of DNA and chromatin [J. Komura and A.D.Riggs, Nucleic Acids Res.,26, 1807-1811 (1998)]. When preceded by reverse transcription (RT), TDPCR provides an extremely sensitive, versatile, quantitative and nucleotide-level assay for detecting RNA lesions or structures that block primer extension during the RT step. The procedure is: (i) RT using a gene-specific oligonucleotide; (ii) ribo-tailing of the single-stranded cDNA product by use of terminal deoxy-nucleotidyl transferase; (iii) ligation of a DNA linker to the tailed cDNA by use of T4 DNA ligase; and (iv) PCR using a nested, gene-specific primer and a linker-specific primer. This procedure combines the versatility of a primer extension assay with nucleotide-level resolution, the specificity of nested primers and the sensitivity of PCR. Band patterns obtained are reproducible and quantifiable. We successfully used the technique for the study of yeast RNA structure, splicing intermediates and ribozyme cleavage. Also, in vivo footprint experiments, using mammalian cells and RNase T1, revealed the binding of iron-responsive element binding protein to iron responsive elements in the mRNAs of transferrin receptor and ferritin H-chain.
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PMID:In vivo, high-resolution analysis of yeast and mammalian RNA-protein interactions, RNA structure, RNA splicing and ribozyme cleavage by use of terminal transferase-dependent PCR. 1071 Apr 33

Iron-responsive elements (IREs), a natural group of mRNA-specific sequences, bind iron regulatory proteins (IRPs) differentially and fold into hairpins [with a hexaloop (HL) CAGUGX] with helical distortions: an internal loop/bulge (IL/B) (UGC/C) or C-bulge. C-bulge iso-IREs bind IRP2 more poorly, as oligomers (n = 28-30), and have a weaker signal response in vivo. Two trans-loop GC base pairs occur in the ferritin IRE (IL/B and HL) but only one in C-bulge iso-IREs (HL); metal ions and protons perturb the IL/B [Gdaniec et al. (1998) Biochemistry 37, 1505-1512]. IRE function (translation) and physical properties (T(m) and accessibility to nucleases) are now compared for IL/B and C-bulge IREs and for HL mutants. Conversion of the IL/B into a C-bulge by a single deletion in the IL/B or by substituting the HL CG base pair with UA both derepressed ferritin synthesis 4-fold in rabbit reticulocyte lysates (IRP1 + IRP2), confirming differences in IRP2 binding observed for the oligomers. Since the engineered C-bulge IRE was more helical near the IL/B [Cu(phen)(2) resistant] and more stable (T(m) increased) and the HL mutant was less helical near the IL/B (ribonuclease T1 sensitive) and less stable (T(m) decreased), both CG trans-loop base pairs contribute to maximum IRP2 binding and translational regulation. The (1)H NMR spectrum of the Mg-IRE complex revealed, in contrast to the localized IL/B effects of Co(III) hexaammine observed previously, perturbation of the IL/B plus HL and interloop helix. The lower stability and greater helix distortion in the ferritin IL/B-IRE compared to the C-bulge iso-IREs create a combinatorial set of RNA/protein interactions that control protein synthesis rates with a range of signal sensitivities.
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PMID:Internal loop/bulge and hairpin loop of the iron-responsive element of ferritin mRNA contribute to maximal iron regulatory protein 2 binding and translational regulation in the iso-iron-responsive element/iso-iron regulatory protein family. 1082 99

Terminal transferase-dependent polymerase chain reaction (TDPCR) can be used after reverse transcription (RT) to analyze RNA. This method (RT-TDPCR) has been used for study of RNA structure and RNA-protein interactions at nucleotide-level resolution. A detailed protocol of RT-TDPCR is presented here with examples of its use with ribonuclease T1 in mammalian cells for detecting (1) RNA structure and protein footprints of the human ferritin heavy-chain messenger RNA and (2) in vivo structure of exon 4 of human XIST (X chromosome inactivation-specific transcript) RNA.
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PMID:Analysis of RNA structure and RNA-protein interactions in mammalian cells by use of terminal transferase-dependent PCR. 1898