Published online 2 September 2008
Haematologica, Vol 93, Issue 12, 1868-1876 doi:10.3324/haematol.13490
Copyright © 2008 by Ferrata Storti Foundation
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Thalassemia Syndrome

Controlling {alpha}-globin: a review of {alpha}-globin expression and its impact on β-thalassemia

Hsiao Phin Joanna Voon, Jim Vadolas

Cell and Gene Therapy Research Group, The Murdoch Children’s Research Institute, The University of Melbourne, Royal Children’s Hospital, Parkville, Melbourne, Australia

Correspondence: Hsiao Phin Joanna Voon, Cell and Gene Therapy Research Group, The Murdoch Children’s Research Institute, The University of Melbourne, Royal Children’s Hospital, Flemington Road, Parkville 3052, Melbourne, Australia. E-mail:joanna.voon{at}mcri.edu.au

Synthesis of {alpha}-globin and {alpha}-globin subunits of hemoglobin occurs at high levels during erythrocyte differentiation in a tightly controlled and coordinated fashion. Expression of {alpha}-globin is a fascinatingly complex process which has been meticulously defined in several recent studies, from chromatin modifications to Pol II recruitment. Following this, {alpha}-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 {alpha}-globin. However, translation of {alpha}-globin at levels exceeding {alpha}-globin expression damages cellular membranes and results in β-thalassemia. It is, therefore, crucial that {alpha}-globin proteins are properly folded and stabilized, processes which are dependent on the presence of haem and AHSP. The exceedingly well-characterized process of {alpha}-globin expression elegantly illustrates the complex interaction of factors which are required to balance necessary high expression against the negative impacts of overexpression.

Key words: hemoglobin, {alpha}-globin, thalassemia.