A model for the structure and functions of iron-responsive elements

doi:10.1016/0378-1119(88)90145-X

Gene

Volume 72, Issues 1–2, 10 December 1988, Pages 201-208

https://doi.org/10.1016/0378-1119(88)90145-X Get rights and content

Abstract

Most eukaryotic cells express two proteins, whose biosynthetic rates are determined by the intracellular iron status. The genes for both these proteins, ferritin and the transferrin receptor (TfR), are regulated at the post-transcriptional level, but by entirely different mechanisms. Ferritin mRNA levels are not affected by acute changes in iron availability. Ferritin biosynthesis is regulated translationally via a defined element contained within the 5' untranslated region (UTR) of the ferritin mRNA. This element has been highly conserved during evolution and has been termed an iron-responsive element (IRE). In contrast to ferritin, the regulation of TfR biosynthesis is mirrored by equivalent changes in TfR mRNA levels. The genetic information for this regulation is mostly located in the region of the gene encoding the 3' UTR of the TfR mRNA. Five elements that closely resemble the ferritin IRE are contained within the region which is critical for TfR regulation. The IRE is suggested to function by forming a specific stem-loop structure that interacts with a transacting factor in an iron-dependent fashion. We present a model that accommodates the mediation of distinct post-transcriptional regulatory phenomena via IREs.

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^☆: Presented at the EMBO/INSERM Workshop on ‘Regulation of Gene Expression by RNA Structure and Anti-messengers’, Les Arcs, Savoie (France) 28 February–4 March 1988.

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A model for the structure and functions of iron-responsive elements☆

Abstract

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Cell

J. Biol. Chem.

Both subunits of rat liver ferritin are regulated at a translational level by iron induction

Nucleic Acids Res.

Iron regulates ferritin mRNA translation through a segment of its 5' untranslated region

Two genetic loci participate in the regulation by iron of the gene for the human transferrin receptor

Iron-responsive elements: regulatory RNA sequences that control mRNA levels and translation

Science

Isolation of cDNA and genomic clones for chicken transferrin receptor

J. Cell Biol.

Supercoil sequencing: a fast simple method for sequencing plasmid DNA

DNA

Structure of gene and pseudogenes of human apoferritin H

Nucleic Acids Res.

Cloning, characterization, expression, and chromosomal localization of a human ferritin heavy-chain gene

A cis-acting element is necessary and sufficient for translational regulation of human ferritin expression in response to iron