Proceedings of the National Academy of Sciences - PNAS, 2012-05, Vol.109 (22), p.8417-8422
2012
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Fe2+ binds iron responsive element-RNA, selectively changing protein-binding affinities and regulating mRNA repression and activation
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2012-05, Vol.109 (22), p.8417-8422
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2012
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Iron increases synthesis rates of proteins encoded in iron-responsive element (IRE)-mRNAs; metabolic iron ("free," "labile") is Fe2+. The noncoding IRE-RNA structure, approximately 30 nt, folds into a stem loop to control synthesis of proteins in iron trafficking, cell cycling, and nervous system function. IRE-RNA riboregulators bind specifically to iron-regulatory proteins (IRP) proteins, inhibiting ribosome binding. Deletion of the IRE-RNA from an mRNA decreases both IRP binding and IRP-independent protein synthesis, indicating effects of other "factors." Current models of IRE-mRNA regulation, emphasizing iron-dependent degradation/modification of IRP, lack answers about how iron increases IRE-RNA/IRP protein dissociation or how IRE-RNA, after IRP dissociation, influences protein synthesis rates. However, we observed Fe2+ (anaerobic) or Mn2+ selectively increase the IRE-RNA/IRP KD. Here we show: (i) Fe2+ binds to the IRE-RNA, altering its conformation (by 2-aminopurine fluorescence and ethidium bromide displacement); (ii) metal ions increase translation of IRE-mRNA in vitro; (iii) eukaryotic initiation factor (eIF)4F binds specifically with high affinity to IRE-RNA; (iv) Fe2+ increased eIF4F/IRE-RNA binding, which outcompetes IRP binding; (v) exogenous eIF4F rescued metal-dependent IRE-RNA translation in eIF4F-depeleted extracts. The regulation by metabolic iron binding to IRE-RNA to decrease inhibitor protein (IRP) binding and increase activator protein (eIF4F) binding identifies IRE-RNA as a riboregulator.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.1120045109Titel-ID: cdi_pnas_primary_109_22_8417
- Format
- –
- Schlagworte
- 2-Aminopurine - chemistry, Base Sequence, Binding Sites, dissociation, Ethidium - chemistry, Eukaryotic Initiation Factor-4F - chemistry, Eukaryotic Initiation Factor-4F - metabolism, Ferritins, Fluorescence, Gene Expression Regulation, Iron, Iron - chemistry, Iron - metabolism, Iron regulatory proteins, Iron-Regulatory Proteins - chemistry, Iron-Regulatory Proteins - metabolism, Messenger RNA, Metal ions, Models, Genetic, Models, Molecular, nervous system, Nucleic Acid Conformation, Physical Sciences, Protein Binding, Protein metabolism, Protein Structure, Tertiary, Protein synthesis, proteins, Response Elements, RNA, RNA - chemistry, RNA - genetics, RNA - metabolism, RNA, Messenger - chemistry, RNA, Messenger - genetics, RNA, Messenger - metabolism