Equal stabilities of normal β globin and nontranslatable β° -39 thalassemic transcripts in cell-free extracts

Abstract

Patients with β° thalassemia arising from premature terminator codon mutations in the gene for β globin do not produce β globin protein; these individuals also exhibit a decreased amount of β globin mRNA in their erythroid cells. The absence of β globin protein is readily explained by the inability of the β°-39 mRNA to be translated. The decrease in β globin mRNA has been attributed to either decreased cytoplasmic stability of the nontranslatable mRNA or to an undefined nuclear lesion. To compare directly the relative stabilities of normal and β°-39 thalassemic globin transcripts, we prepared normal and thalassemia β globin pre-mRNAs and mRNAs using cloned DNA templates and the SP6 promoter-polymerase system. The stability of the transcripts was assessed by incubation in various cell-free extracts. Our results indicate that although the stabilities of the β globin transcripts varied considerably from one extract to another the stabilities of the β°-39 thalassemic pre-mRNAs and mRNAs were equal to those of normal β globin mRNAs in every extract tested.