Decreased α Globin Messenger RNA Activity associated with Polyribosomes in α Thalassaemia

Abstract

IN the α thalassaemia syndromes, there is decreased production of structurally normal α globin chains¹. Two types of α thalassaemia genes are postulated, α-1 leading to absent production of α chains and α-2 resulting in decreased production of α chains^1,2. Haemoglobin H (HbH) disease seems to result from double heterozygosity for α-l and α-2 genes. In HbH disease, the red cells of affected patients have detectable HbH, a tetramer consisting of four β chains due to the relative deficiency of α chain synthesis. Reticulocytes from these patients, when incubated with radioactive amino-acids, synthesize two to four times as much β chain as α chain^3–6. The study described here was undertaken to determine if the defect in a thalassaemia could be localized to the α chain mRNA in these cells. The results indicate that mRNA isolated from the polyribosomes of a patient with HbH disease reproduces the defect in α chain synthesis when added to a cell-free system. Thus, in HbH disease, α chain mRNA associated with polyribosomes is either decreased in amount or abnormal. These findings are comparable with those previously reported in β thalassaemia in which decreased polyribosomal globin mRNA activity was demonstrated (refs. 7–9 and unpublished results of L. W. D. and A. B. with M. T., P. A. Marks and S. Metafora).