| Full text | |
| Author(s): |
dos Santos, Camila O.
[1]
;
Dore, Louis C.
[1]
;
Valentine, Eric
[1]
;
Shelat, Suresh G.
[2]
;
Hardison, Ross C.
[3]
;
Ghosh, Manik
[4]
;
Wang, Wei
[5]
;
Eisenstein, Richard S.
[6]
;
Costa, Fernando F.
[7]
;
Weiss, Mitchell J.
[1]
Total Authors: 10
|
| Affiliation: | [1] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 - USA
[2] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 - USA
[3] Penn State Univ, Dept Biochem & Mol Biol, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 - USA
[4] NICHD, NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 - USA
[5] Wake Forest Univ Hlth Sci, Dept Biochem, Winston Salem, NC 27157 - USA
[6] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 - USA
[7] Univ Estadual Campinas, Ctr Hemotherapy & Hematol, Sao Paulo - Brazil
Total Affiliations: 7
|
| Document type: | Journal article |
| Source: | Journal of Biological Chemistry; v. 283, n. 40, p. 26956-26964, OCT 3 2008. |
| Web of Science Citations: | 33 |
| 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. (AU) | |
| FAPESP's process: | 02/13801-7 - Hereditary hemoglobin disorders: molecular genetics, clinical features and animal models with the production of transgenic animals |
| Grantee: | Fernando Ferreira Costa |
| Support Opportunities: | Research Projects - Thematic Grants |