Translational profiles of alpha 1-, alpha 2-, and beta-globin messenger ribonucleic acids in human reticulocytes

Abstract

In human reticulocytes, the critical balancing of alpha- and beta-globin synthesis may be controlled in part by differential translation of the three major adult globin messenger RNAs (mRNAs), alpha 1, alpha 2, and beta. In this study, we determined, as a parameter of translational efficiency, the relative ribosome loading of these three mRNAs. Using oligonucleotide probes specific for the alpha 1- and alpha 2-globin mRNAs, we find that these two mRNAs have identical translational profiles. Their distribution contrasts with that of beta-globin mRNA, which is present on heavier polyribosomes and is less prevalent in pre-80S messenger ribonucleoprotein fractions. The relative distribution of alpha- vs. beta-globin mRNA is consistent with more efficient beta-globin translation. In contrast, the parallel distributions of alpha 1- and alpha 2-globin mRNAs suggests they are translated with equal efficiencies. Considering the relative concentrations of the two alpha-globin mRNAs in normal reticulocytes, this result predicts a dominant role for the alpha 2-globin locus in human alpha-globin expression.