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PMID: 2050126 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Identification of a novel iron-responsive element in murine and human erythroid delta-aminolevulinic acid synthase mRNA.

The EMBO journal ·Vol. 10 ·No. 7 ·1991-07-00 ·Pages 1903-9

Dandekar T, Stripecke R, Gray NK, Goossen B, Constable A, Johansson HE, Hentze MW

Abstract

Iron-responsive elements (IREs) are regulatory RNA elements which are characterized by a phylogenetically defined sequence-structure motif. Their biological function is to provide a specific binding site for the IRE-binding protein (IRE-BP). Iron starvation of cells induces high affinity binding of the cytoplasmic IRE-BP to an IRE which has at least two different known biological consequences, repression of ferritin mRNA translation and stabilization of the transferrin receptor transcript. We report the identification of a novel, evolutionarily conserved IRE motif in the 5' UTR of murine and human erythroid-specific delta-aminolevulinic acid synthase (eALAS) mRNA which encodes the first, and possibly rate limiting, enzyme of the heme biosynthetic pathway. We demonstrate the function of the eALAS IRE as a specific binding site for the IRE-BP by gel retardation analyses and by in vitro translation experiments. In addition, we show that the 5' UTR of eALAS mRNA is sufficient to mediate iron-dependent translational regulation in vivo. These findings strongly suggest involvement of the IRE-IRE-BP system in the control of heme biosynthesis during erythroid differentiation.

MeSH Terms
5-Aminolevulinate Synthetase/blood,genetics Animals Base Sequence Carrier Proteins/blood,genetics Cell-Free System/metabolism Databases, Factual Erythroid Precursor Cells/enzymology,physiology Ferritins/metabolism Fibroblasts/enzymology Humans Iron-Regulatory Proteins Mice Mice, Inbred C57BL Molecular Sequence Data Nucleic Acid Conformation Oxidation-Reduction Placenta Protein Biosynthesis RNA, Messenger/blood,chemistry,metabolism
Chemicals
Carrier Proteins Iron-Regulatory Proteins RNA, Messenger Ferritins 5-Aminolevulinate Synthetase
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Dandekar T
European Molecular Biology Laboratory, Heidelberg FRG.
Stripecke R
Gray N K
Goossen B
Constable A
Johansson H E
Hentze M W
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1991-07-00
Pages
1903-9
Language
English
Region
England
NLM ID
8208664
PMCID
PMC452865
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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