An iron responsive element-like stem-loop regulates alpha-hemoglobin-stabilizing protein mRNA.
J Biol Chem
; 283(40): 26956-64, 2008 Oct 03.
Article
em En
| MEDLINE
| ID: mdl-18676996
ABSTRACT
Hemoglobin production during erythropoiesis is mechanistically coupled to the acquisition and metabolism of iron. We discovered that iron regulates the expression of alpha-hemoglobin-stabilizing protein (AHSP), a molecular chaperone that binds and stabilizes free alpha-globin during hemoglobin synthesis. In primates, the 3'-untranslated region (UTR) of AHSP mRNA contains a nucleotide sequence resembling iron responsive elements (IREs), stem-loop structures that regulate gene expression post-transcriptionally by binding iron regulatory proteins (IRPs). The AHSP IRE-like stem-loop deviates from classical consensus sequences and binds IRPs poorly in electrophoretic mobility shift assays. However, in cytoplasmic extracts, AHSP mRNA co-immunoprecipitates with IRPs in a fashion that is dependent on the stem-loop structure and inhibited by iron. Moreover, this interaction enhances AHSP mRNA stability in erythroid and heterologous cells. Our findings demonstrate that IRPs can regulate mRNA expression through non-canonical IREs and extend the repertoire of known iron-regulated genes. In addition, we illustrate a new mechanism through which hemoglobin may be modulated according to iron status.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Sanguíneas
/
Chaperonas Moleculares
/
Regiões 3' não Traduzidas
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Estabilidade de RNA
/
Eritropoese
/
Ferro
Limite:
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos