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Articles by Camila O. dos Santos
Total Records ( 1 ) for Camila O. dos Santos
  Camila O. dos Santos , Louis C. Dore , Eric Valentine , Suresh G. Shelat , Ross C. Hardison , Manik Ghosh , Wei Wang , Richard S. Eisenstein , Fernando F. Costa and Mitchell J. Weiss
  Hemoglobin production during erythropoiesis is mechanistically coupled to the acquisition and metabolism of iron. We discovered that iron regulates the expression of α-hemoglobin-stabilizing protein (AHSP), a molecular chaperone that binds and stabilizes free α-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.
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