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Cited by 297RNA and protein synthesis mechanismsIron Metabolism and DisordersRNA Research and Splicing

IRP-1 binding to ferritin mRNA prevents the recruitment of the small ribosomal subunit by the cap-binding complex eIF4F.

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Muckenthaler, Martina, Gray, Nicola K, Hentze, Matthias W·1998·Molecular Cell
DOI 10.1016/s1097-2765(00)80282-8
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Abstract

Binding of iron regulatory proteins (IRPs) to IREs located in proximity to the cap structure of ferritin H- and L-chain mRNAs blocks ferritin synthesis by preventing the recruitment of the small ribosomal subunit to the mRNA. We have devised a novel procedure to examine the assembly of translation initiation factors (eIFs) on regulated mRNAs. Unexpectedly, we find that the cap binding complex eIF4F (comprising eIF4E, eIF4G, and eIF4A) assembles even when IRP-1 is bound to the cap-proximal IRE. This assembly is futile, because bridging interactions between eIF4F and the small ribosomal subunit cannot be established in the presence of IRP-1. Our findings provide insight into translational control by an mRNA binding protein at the level of translation initiation factors and uncover a key regulatory step in iron homeostasis.

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  • Muckenthaler and colleagues showed that IRP binding sterically blocks recruitment of the small ribosomal subunit to the initiation complex, thus preventing translation.

    “Muckenthaler and colleagues showed that IRP binding sterically blocks recruitment of the small ribosomal subunit to the initiation complex, thus preventing translation.38”

    From Forging a field: the golden age of iron biology. (2008) · cites this paper as [38]

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Authors
Muckenthaler, M., Gray, N. K., & Hentze, M. W.
Affiliations
European Molecular Biology Laboratory (DE)
Corresponding author
Hentze, Matthias W
ORCID
Venue
Molecular Cell
Publisher
Elsevier BV
Published
1998-09
Volume
2
Issue
3
Pages
383-388
ISSN
1097-2765 (ISSN-L)
DOI
10.1016/s1097-2765(00)80282-8
OpenAlex
W2142282262
Cited by
297
References
40
Citations by year
2026: 5 · 2025: 10 · 2024: 12 · 2023: 12 · 2022: 9 · 2021: 8 · 2020: 7 · 2019: 10 · 2018: 3 · 2017: 6 · 2016: 5 · 2015: 4 · 2014: 8 · 2013: 5 · 2012: 9
FWCI
5.66
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Cell (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
ferritin mRNA, iron regulatory element, eIF4F, translation initiation factors, mRNA cap binding, iron homeostasis, translational regulation, eIF4E, eIF4G, eIF4A
MeSH terms
Animals, Binding Sites, Ferritins, Humans, Iron-Sulfur Proteins, Models, Genetic, Models, Molecular, Peptide Chain Initiation, Translational, Peptide Initiation Factors, Rabbits, Reticulocytes, Ribosomes, RNA Caps, RNA, Messenger, Protein Biosynthesis, RNA-Binding Proteins, Iron-Regulatory Proteins, Iron Regulatory Protein 1, Eukaryotic Initiation Factor-4F

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