Oxidation of guanines in the iron-responsive element RNA: similar structures from chemical modification and recent NMR studies
| Autor: | Suzanne A. Ciftan, Elizabeth C. Theil, H. Holden Thorp |
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| Rok vydání: | 1998 |
| Předmět: |
Models
Molecular iron-responsive element Guanine Magnetic Resonance Spectroscopy Reticulocytes Base pair Stereochemistry Iron Clinical Biochemistry chemical nuclease Biochemistry chemistry.chemical_compound Drug Discovery Protein biosynthesis Animals RNA Messenger Nucleic acid structure RNA structure Molecular Biology Pharmacology Oligonucleotide RNA General Medicine Nuclear magnetic resonance spectroscopy DNA RNA-protein recognition chemistry Protein Biosynthesis Molecular Medicine Nucleic Acid Conformation Rabbits guanine oxidation Oxidation-Reduction |
| Zdroj: | Chemistrybiology. 5(12) |
| ISSN: | 1074-5521 |
| Popis: | Background: The translation or stability of the mRNAs from ferritin, m-aconitase, erythroid aminoevulinate synthase and the transferrin receptor is controlled by the binding of two iron regulatory proteins to a family of hairpin-forming RNA sequences called iron-responsive elements (IREs). The determination of higher-solution nuclear magnetic resonance (NMR) structures of IRE variants suggests an unusual hexaloop structure, leading to an intra-loop G-C base pair and a highly exposed loop guanine, and a special internal loop/bulge in the ferritin IRE involving a shift in base pairing not predicted with standard algorithms. Results: Cleavage of synthetic 55- and 30-mer RNA oligonucleotides corresponding to the ferritin IRE with complexes based on oxoruthenium(IV) shows enhanced reactivity at a hexaloop guanine and at a guanine adjacent to the internal loop/bulge with strong protection at a guanine in the internal loop/bulge. These results are consistent with the recent NMR structures. The synthetic 55-mer RNA binds the iron-regulatory protein from rabbit reticulocyte lysates. The DNA analogs of the 55- and 30-mers do not show the same reactivity pattern. Conclusions: The chemical reactivity of the guanines in the ferritin IRE towards oxoruthenium(IV) supports the published NMR structures and the known oxidation chemistry of the metal complexes, The results constitute progress towards developing stand-alone chemical nucleases that reveal significant structural properties and provide results that can ultimately be used to constrain molecular modeling. |
| Databáze: | OpenAIRE |
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