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Human alpha-globin gene expression. The dominant role of the alpha 2-locus in mRNA and protein synthesis.

Liebhaber, S A, Cash, F E, Ballas, S K·1986·Journal of Biological Chemistry
DOI 10.1016/s0021-9258(18)66871-1
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Abstract

The two human alpha-globin genes, alpha 1 and alpha 2, are coexpressed in normal erythroid cells and encode identical alpha-globin protein products. Based upon genetic studies, it has been assumed that these two adjacent and highly homologous genes are equally expressed. In previous studies we have, however, demonstrated that the alpha 2 gene encodes a 2-3-fold higher steady state level of mRNA than the alpha 1 gene. In the present study, we monitor the relative levels of protein production from these two loci by quantitating the synthesis of specific alpha-globin structural mutants encoded by each alpha-globin gene. These values are then used to infer the relative contributions of the normal alpha 1 and alpha 2 loci to total alpha-globin production. The results of eight separate studies, each based upon a different alpha-globin structural mutant mapped to either the alpha 1 or the alpha 2 locus, are internally consistent. The data demonstrate that the alpha 2 gene encodes 2-3-fold more protein than the alpha 1 gene. These results suggest that the human alpha-globin gene cluster contains a major and a minor locus. The dominant expression of the alpha 2 gene predicts a greater impact of mutations at this locus, in comparison to mutations at the alpha 1 locus, in the generation of the alpha-thalassemia phenotype.

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Metadata

Authors
Liebhaber, S. A., Cash, F. E., & Ballas, S. K.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1986-11
Volume
261
Issue
32
Pages
15327-15333
ISSN
0021-9258
DOI
10.1016/s0021-9258(18)66871-1
Cited by
113
References
0
Language
en
Licence

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