An iron responsive element-like stem-loop regulates alpha-hemoglobin-stabilizing protein mRNA.

dos Santos, Camila O, Dore, Louis C, Valentine, Eric, Shelat, Suresh G, Hardison, Ross C, Ghosh, Manik, Wang, Wei, Eisenstein, Richard S, Costa, Fernando F, Weiss, Mitchell J (October 2008) An iron responsive element-like stem-loop regulates alpha-hemoglobin-stabilizing protein mRNA. Journal of Biological Chemistry, 283 (40). pp. 26956-26964. ISSN 0021-9258

URL: https://www.ncbi.nlm.nih.gov/pubmed/18676996
DOI: 10.1074/jbc.M802421200

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.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA regulation
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > red blood cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > red blood cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > red blood cells
CSHL Authors:
Communities: CSHL labs > Dos Santos lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 3 October 2008
Date Deposited: 20 May 2021 20:29
Last Modified: 20 May 2021 20:29
PMCID: PMC2555993
URI: https://repository.cshl.edu/id/eprint/40109

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