Initiation of globin synthesis in beta-thalassemia.

Abstract

The mechanism of initiation of human globin chains was examined to determine if the initiation of protein synthesis is abnormal in β-thalassemia. Messenger RNA (mRNA) was isolated from the reticulocytes of normal adults, newborn infants and patients with β-thalassemia to study synthesis of alpha, beta and gamma chains. These isolated mRNA preparations were assayed in a cell-free system derived from rabbit reticulocytes. The initial dipeptides formed during the synthesis of the alpha and beta chains were determined. In normal subjects and patients with β-thalassemia the dipeptide for both the alpha and beta chains was found to be methionine-valine. The initial dipeptide for the gamma chain, determined in newborn infants and in patients with β-thalassemia, was methionine-glycine in both. All mRNA's studied shared a common requirement for methionyl-tRNAF (the specific initiator tRNA) and for the protein initiation factors. By these criteria, the mechanism of globin-chain initiation in β-thalassemia is normal. (N Engl J Med 288:1091–1096, 1973)