Translation of β-Globin m-RNA in β-Thalassemia and the S and C Hemoglobinopathies

Abstract

Genetic and biochemical evidence indicates that in β-thalassemia there is impaired synthesis of the β-globin chains of hemoglobin A. In patients heterozygous for the hemoglobinopathies, hemoglobin S and hemoglobin C, the mutant β-chain is produced in smaller amounts than normal β^A. Defective m-RNA translation has been suggested as a possible cause of decreased β-globin polypeptide synthesis in thalassemia and the hemoglobinopathies. In the present study, the ribosomal assembly of β-globin chains was examined in the peripheral, nucleated red blood cells and reticulocytes of patients with Cooley's anemia, thalassemia intermedia, sickle thalassemia, sickle cell anemia, hemoglobin C disease, and in hemolytic anemias not associated with a hemoglobinopathy. The translation times of β^A, β^S, and β^C did not differ significantly (average times; β^A = 75 sec, range 43-114, β^S = 69 sec, β^C = 92 sec). In thalassemia, no evidence was found for a delay in translation as the cause of the marked impairment of β-globin synthesis. In several specimens of peripheral blood from thalassemic patients, the translation time of the β-chain was even shorter than in nonthalassemic specimens (average time = 45 sec, range 35-59). The results suggest that the defect in β-globin synthesis in β-thalassemia is due to impaired initiation of β-globin chain assembly or a quantitative deficiency in m-RNA.