Equal Stabilities of Normal β Globin and Nontranslatable β°-39 Thalassemic Transcripts in Cell-Free Extracts

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 βglobin 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 thalas- semic 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.© 1987 by Grune & Stratton, Inc. 0006-4971/87/7001-0047$3.00/0