The 5′-Untranslated Region of Human Transferrin mRNA, Which Contains a Putative Iron-Regulatory Element, Is Bound by Purified Iron-Regulatory Protein in a Sequence-Specific Manner

Human transferrin mRNA contains a 5′-untranslated region that (1) has homology to an iron responsive element and (2) is implicated in translational iron regulation of human transferrin transgenes in transgenic mice. Ferritin mRNA contains a 5′-untranslated region iron-responsive element, but iron re...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1995-07, Vol.212 (3), p.925-932
Main Authors: Cox, L.A., Kennedy, M.C., Adrian, G.S.
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Binding Sites - genetics
Cytoplasm - metabolism
Ferritins - genetics
Humans
In Vitro Techniques
Iron - metabolism
Iron-Regulatory Proteins
Liver - metabolism
Mice
Mice, Transgenic
Molecular Sequence Data
Mutation
Nucleic Acid Conformation
RNA, Messenger - chemistry
RNA, Messenger - genetics
RNA, Messenger - metabolism
RNA-Binding Proteins - chemistry
RNA-Binding Proteins - genetics
RNA-Binding Proteins - metabolism
Transferrin - genetics
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Summary:Human transferrin mRNA contains a 5′-untranslated region that (1) has homology to an iron responsive element and (2) is implicated in translational iron regulation of human transferrin transgenes in transgenic mice. Ferritin mRNA contains a 5′-untranslated region iron-responsive element, but iron regulation of ferritin differs from that of human transferrin transgenes in both magnitude and direction. Structural differences between the ferritin iron-responsive element and the human transferrin putative iron-responsive element may influence their iron-regulatory protein interactions and direct the differing translational responses. This study examines human transferrin RNA nucleotide sequence requirements for binding of cytoplasmic proteins and purified iron-regulatory protein. Mutations of the putative transferrin iron-responsive element similarly affected binding of purified iron-regulatory protein and liver cytoplasmic proteins, providing evidence that the IRP is one of the liver cytoplasmic proteins that binds the human transferrin iron-regulatory element and suggesting that it may be involved in iron-regulation of transferrin.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1995.2058