Controlling alpha-globin: a review of alpha-globin expression and its impact on beta-thalassemia.
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 beta-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.
Voon
Hsiao Phin Joanna
HP
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. joanna.voon@mcri.edu.au
Vadolas
Jim
J