Protein Synthesis in Cell-free Systems from Reticulocytes of Thalassaemic Patients

Abstract

β-THALASSAEMIA is a hereditary anaemia, characterized by a selective decrease in the synthesis of normal β-globin chains¹. It is not known, however, whether the defect in cells of patients with β-thalassaemia results from a deficiency in the amount of messenger RNA (mRNA) for β-globin chains or a defect at the level of protein synthesis on the polyribosomes. Previous studies in intact cells indicated that a defect exists at the level of the ribosome–mRNA complex in reticulocytes from patients with thalassaemia². Subsequent investigations using a cell-free system confirmed these findings and demonstrated that the ribosomes had a normal capacity to respond to the addition of a synthetic messenger, poly U³. Recent experiments by Clegg and his co-workers demonstrated that the synthetic time for a single β chain is similar in thalassaemic and non-thalassaemic cells⁴. Taken together, these findings suggest that the defect in β chain synthesis which characterizes thalassaemia arises from either a diminution in the amount of mRNA or an abnormality in the initiation of β chains in these cells. The present studies were designed to investigate more closely some of the events concerned with the initiation of synthesis of polypeptide chains by the ribosome–mRNA complex in red cells from thalassaemic and non-thalassaemic patients.