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Iron regulatory protein prevents binding of the 43S translation pre‐initiation complex to ferritin and eALAS mRNAs.
Open accessAbstract
Translation of ferritin and erythroid 5-aminolevulinate synthase (eALAS) mRNAs is regulated by iron via mRNA-protein interactions between iron-responsive elements (IREs) and iron regulatory protein (IRP). In iron-depleted cells, IRP binds to single IREs located in the 5' untranslated regions of ferritin and eALAS mRNAs and represses translation initiation. The molecular mechanism underlying this translational repression was investigated using reconstituted, IRE-IRP-regulated, cell-free translation systems. The IRE-IRP interaction is shown to prevent the association of the 43S translation pre-initiation complex (including the small ribosomal subunit) with the mRNA. Studies with the spliceosomal protein U1A and mRNAs which harbour specific binding sites for this protein in place of an IRE furthermore reveal that the 5' termini of mRNAs are generally sensitive to repressor protein-mediated inhibition of 43S pre-initiation complex binding.
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Metadata
- Authors
- Gray, N. K., & Hentze, M. W.
- Affiliations
- European Molecular Biology Laboratory (DE)
- Venue
- The EMBO Journal
- Published
- 1994-08-01
- Volume
- 13
- Issue
- 16
- Pages
- 3882-3891
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC395301
- OpenAlex
- W70018918
- Cited by
- 276
- References
- 47
- Citations by year
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- FWCI
- 11.52
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- iron regulatory proteins, iron-responsive element, ferritin mRNA, protein synthesis inhibition, mRNA-protein interactions, 5' untranslated region, U1A, small ribosomal subunit, cell-free translation system
- MeSH terms
- 5-Aminolevulinate Synthetase, Animals, Cell-Free System, Ferritins, Models, Genetic, Peptide Chain Initiation, Translational, Protein Binding, Rabbits, Regulatory Sequences, Nucleic Acid, Repressor Proteins, Reticulocytes, Ribosomes, RNA, Messenger, Chloramphenicol O-Acetyltransferase, RNA-Binding Proteins, Ribonucleoprotein, U1 Small Nuclear, Genes, Reporter, Iron-Regulatory Proteins
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