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Type: Artigo de periódico
Title: An iron responsive element-like stem-loop regulates alpha-hemoglobin-stabilizing protein mRNA
Author: dos Santos, CO
Dore, LC
Valentine, E
Shelat, SG
Hardison, RC
Ghosh, M
Wang, W
Eisenstein, RS
Costa, FF
Weiss, MJ
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.
Country: EUA
Editor: Amer Soc Biochemistry Molecular Biology Inc
Citation: Journal Of Biological Chemistry. Amer Soc Biochemistry Molecular Biology Inc, v. 283, n. 40, n. 26956, n. 26964, 2008.
Rights: fechado
Identifier DOI: 10.1074/jbc.M802421200
Date Issue: 2008
Appears in Collections:Unicamp - Artigos e Outros Documentos

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