Maquat L E, Kinniburgh A J, Rachmilewitz E A, Ross J
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706.
Cell. 1981 Dec;27(3 Pt 2):543-53. doi: 10.1016/0092-8674(81)90396-2.
The molecular defect in four Kurdish Jews with homozygous, mRNA-deficient beta zero thalassemia was investigated. Electrophoretic profiles of pulse-labeled alpha- and beta-globin RNAs are similar to those of non-thalassemics; therefore, at least one of the thalassemic beta-globin alleles is transcribed. During a 30 min actinomycin D chase, most of the alpha- and beta-globin mRNA precursors and processing intermediates are converted to mRNA-sized RNA. Thalassemic and non-thalassemic beta-globin RNAs are indistinguishable, as determined by S1 nuclease mapping and RNA blotting. Non-thalassemic beta-globin mRNA is stable during a 30 min actinomycin chase, but 30%-75% of the thalassemic mRNA-sized molecules is degraded during that period. We conclude that the absence of beta-globin mRNA in this disease results from rapid turnover of beta-globin mRNA-sized molecules.
对四名患有纯合子、mRNA 缺陷型β0地中海贫血的库尔德犹太人的分子缺陷进行了研究。脉冲标记的α-和β-珠蛋白 RNA 的电泳图谱与非地中海贫血患者的相似；因此，至少其中一个地中海贫血β-珠蛋白等位基因被转录。在 30 分钟的放线菌素 D 追踪过程中，大多数α-和β-珠蛋白 mRNA 前体及加工中间体被转化为 mRNA 大小的 RNA。通过 S1 核酸酶图谱分析和 RNA 印迹法确定，地中海贫血和非地中海贫血的β-珠蛋白 RNA 没有区别。在 30 分钟的放线菌素追踪过程中，非地中海贫血的β-珠蛋白 mRNA 是稳定的，但在此期间，30%-75%的地中海贫血 mRNA 大小的分子会被降解。我们得出结论，这种疾病中β-珠蛋白 mRNA 的缺失是由于β-珠蛋白 mRNA 大小分子的快速周转所致。
