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

Abstract

Patients with ß° thalassemia arising from premature terminator codon mutations in the gene for ß globin do not produce ß globin protein; these individuals also exhibit a decreased amount of ß globin mRNA in their erythroid cells. The absence of ß globin protein is readily explained by the inability of the ß°-39 mRNA to be translated. The decrease in ß 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 ß°-39 thalassemic globin transcripts, we prepared normal and thalassemia ß 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 ß globin transcripts varied considerably from one extract to another the stabilities of the ß°-39 thalassemic pre-mRNAs and mRNAs were equal to those of normal ß globin mRNAs in every extract tested.