Different rates of mRNA translation balance the expression of the two human alpha-globin loci.

The relative translational efficiency of the two human alpha-globin mRNAs, alpha 1 and alpha 2, was measured in vitro in a rabbit reticulocyte lysate system. To differentiate the translational products of these two mRNAs which normally encode an identical alpha-globin protein product, we used reticulocyte mRNA from a recently described Chinese subject. In this subject, an electrophoretically distinct alpha-globin mutant is encoded at the alpha 2 locus and both the alpha 1- and alpha 2-globin genes are deleted from the homologous chromosome (--/alpha 125Pro alpha). As in normal controls, the concentration of alpha 2-globin mRNA exceeded alpha 1 by approximately 3-fold. However, alpha 1- and alpha 2-globin proteins were synthesized by this reticulocyte mRNA at equal rates. This data suggests that the equal expression of the two alpha-globin genes observed in human erythrocytes results from a balance between the 3-fold excess of alpha 2-globin mRNA and a 3-fold higher translational efficiency of alpha 1-globin mRNA. The disparate translational efficiencies of the two alpha-globin mRNAs may be determined by the divergent structure of their 3' noncoding regions.