Cited by 276Iron Metabolism and DisordersRNA and protein synthesis mechanismsRNA Research and Splicing

Iron regulatory protein prevents binding of the 43S translation pre‐initiation complex to ferritin and eALAS mRNAs.

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Gray, N.K., Hentze, M.W.·1994·The EMBO Journal

Abstract

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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Crossref · 10.1002/j.1460-2075.1994.tb06699.x

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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
OpenAlex
W70018918
Cited by
276
References
47
Citations by year
2026: 3 · 2025: 2 · 2024: 7 · 2023: 6 · 2022: 7 · 2021: 4 · 2020: 6 · 2019: 7 · 2018: 5 · 2017: 7 · 2016: 5 · 2015: 3 · 2014: 8 · 2013: 2 · 2012: 4
FWCI
11.52
Type
journal article
Language
en
Open access
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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