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
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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