Translation of  -globin m-RNA in  -thalassemia and the S and C hemoglobinopathies.
Genetic and biochemical evidence indicates that in beta-thalassemia there is impaired synthesis of the beta-globin chains of hemoglobin A. In patients heterozygous for the hemoglobinopathies, hemoglobin S and hemoglobin C, the mutant beta-chain is produced in smaller amounts than normal beta(A). Defective m-RNA translation has been suggested as a possible cause of decreased beta-globin polypeptide synthesis in thalassemia and the hemoglobinopathies. In the present study, the ribosomal assembly of beta-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 beta(A), beta(S), and beta(C) did not differ significantly (average times; beta(A) = 75 sec, range 43-114, beta(S) = 69 sec, beta(C) = 92 sec). In thalassemia, no evidence was found for a delay in translation as the cause of the marked impairment of beta-globin synthesis. In several specimens of peripheral blood from thalassemic patients, the translation time of the beta-chain was even shorter than in nonthalassemic specimens (average time = 45 sec, range 35-59). The results suggest that the defect in beta-globin synthesis in beta-thalassemia is due to impaired initiation of beta-globin chain assembly or a quantitative deficiency in m-RNA.
D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000235:genetics / Q000378:metabolism*; D001345:Autoradiography; D002247:Carbon Isotopes; D002648:Child; D004912:Erythrocytes; D005914:Globins / Q000096:biosynthesis*; D006445:Hemoglobin C Disease / Q000235:genetics / Q000378:metabolism*; D006455:Hemoglobins, Abnormal / Q000096:biosynthesis*; D006801:Humans; D010442:Peptide Chain Initiation, Translational; D010455:Peptides / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D012156:Reticulocytes; D012270:Ribosomes; D013789:Thalassemia / Q000235:genetics / Q000378:metabolism*; D014316:Tritium
D002247:Carbon Isotopes; D006455:Hemoglobins, Abnormal; D010455:Peptides; D012333:RNA, Messenger; D014316:Tritium; D005914:Globins