Article

Processing of human β-globin mRNA precursor to mRNA is defective in three patients with β +-thalassemia

Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 08/1980; 77(7):4287-91. DOI: 10.1073/pnas.77.7.4287
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ABSTRACT

Nucleated bone marrow cells from normal individuals and from three patients with homozygous beta+-thalassemia were pulse-labeled with tritiated nucleosides. The processing of the newly synthesized globin mRNA precursors was monitored by inhibiting additional transcription with actinomycin D for 30 min. Human beta-globin mRNA is derived from its precursor via a series of reactions that generate processing intermediates. In nonthalassemic cells the precursor is processed efficiently to mature mRNA during the chase. In contrast, in beta+-thalassemic cells the processing of beta-globin RNA is defective. In one patient the beta-globin mRNA precursor turns over during the chase, but some of the intermediate RNAs accumulate and are not processed to mRNA. In two other patients a large fraction of the precursor and intermediate RNAs is not processed to mRNA. The alpha-globin mRNA precursor and intermediates are processed efficiently to mRNA-sized molecules in thalassemic and normal cells. The reduction in the rate of beta-globin but not alpha-globin RNA processing accounts for the alpha/beta globin mRNA imbalance in thalassemic erythroid cells. We discuss the possibility that the genetic lesions in beta+-thalassemia are at splicing signal sites within intervening sequences of the beta-globin gene.

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Available from: George R Honig, Oct 16, 2014
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    • "of splicing defects that cause a disease, in this case P+thalassemia (Kantor et al. 1980; Maquat et al. 1980). Over the years, it has become clear that sequence elements important for proper intron removal reside in the immediate vicinity of the exon-intron borders (fig. "

    Preview · Article · Sep 1996 · The American Journal of Human Genetics
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    • "Indeed , Beserga and Benz (1988) showed that no reduction in mRNA levels occurred when translatable missense mutations were made in the human beta globin gene in vitro. However, defective RNA processing, such as occurs in human Beta+-thalassemia (Maquat et al ., 1980) can account for decreased mRNA levels (Housman et al., 1973) . "
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