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Start Over Author "Hardison, Ross" Journal journal of biological chemistry
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9. 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, and Weiss MJ

Subjects
3' Untranslated Regions genetics, Blood Proteins genetics, HeLa Cells, Hemoglobins biosynthesis, Hemoglobins genetics, Humans, K562 Cells, Molecular Chaperones genetics, Nucleic Acid Conformation, 3' Untranslated Regions metabolism, Blood Proteins metabolism, Erythropoiesis physiology, Iron metabolism, Molecular Chaperones metabolism, RNA Stability physiology
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.

Published
2008
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