[HTML][HTML] Controlling α-globin: a review of α-globin expression and its impact on β-thalassemia

HPJ Voon, J Vadolas - Haematologica, 2008 - haematologica.org
Haematologica, 2008haematologica.org
Synthesis of α-globin and α-globin subunits of hemoglobin occurs at high levels during
erythrocyte differentiation in a tightly controlled and coordinated fashion. Expression of α-
globin is a fascinatingly complex process which has been meticulously defined in several
recent studies, from chromatin modifications to Pol II recruitment. Following this, α-globin
transcripts are processed and stabilized by a protein complex which binds the 3'untranslated
region. Transcription and stabilization contribute to high level expression of α-globin …
Abstract
Synthesis of α-globin and α-globin subunits of hemoglobin occurs at high levels during erythrocyte differentiation in a tightly controlled and coordinated fashion. Expression of α-globin is a fascinatingly complex process which has been meticulously defined in several recent studies, from chromatin modifications to Pol II recruitment. Following this, α-globin transcripts are processed and stabilized by a protein complex which binds the 3’untranslated region. Transcription and stabilization contribute to high level expression of α-globin. However, translation of α-globin at levels exceeding α-globin expression damages cellular membranes and results in β-thalassemia. It is, therefore, crucial that α-globin proteins are properly folded and stabilized, processes which are dependent on the presence of haem and AHSP. The exceedingly well-characterized process of α-globin expression elegantly illustrates the complex interaction of factors which are required to balance necessary high expression against the negative impacts of overexpression.
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