Relative stability of alpha- and beta-globin messenger RNAs in homozygous beta+ thalassemia

Abstract

The relative concentrations of alpha-, beta-, and gamma-globin mRNA sequences were measured in bone marrow nuclear and cytoplasmic RNA and in RNA from peripheral blood reticulocytes of three patients with homozygous beta+ thalassemia. Our results suggest that the quantitative deficiency in beta-globin mRNA may arise because of abnormal metabolism of molecules containing beta mRNA sequences. Complementary DNAs specific for each of the globins were synthesized. Variable quantities of RNA were incubated to equilibrium with 3H-labeled alpha- and 32P-labeled beta- or gamma-enriched cDNA. We found for each of the patients that the alpha/beta mRNA sequence ratio was more nearly normal in the nuclear RNA than in either cytoplasmic or reticulocyte RNA. Conversely, gamma mRNA sequences were very low in the nucleus with an increase in the relative concentration in both cytoplasm and reticulocyte RNA. The thermal stability of nucleic acid duplexes formed between beta cDNA and nuclear RNA from one patient with beta+ thalassemia was equivalent to that of duplexes formed with normal nuclear RNA. Approximately equal amounts of thalassemic alpha and beta mRNA were retained by oligo(dT)-cellulose, indicating that the 3' poly(A) segment was present on both. Our results indicate that beta-globin mRNA, although grossly normal in structure, fails to accumulate in beta+ thalassemic erythroid cells in amounts equivalent to the mRNA for alpha-globin.