• Medientyp: E-Artikel
  • Titel: Processing of Human β -globin mRNA Precursor to mRNA is Defective in Three Patients with β+-thalassemia
  • Beteiligte: Maquat, Lynne E.; Kinniburgh, Alan J.; Beach, Larry R.; Honig, George R.; Lazerson, Jack; Ershler, William B.; Ross, Jeffrey
  • Erschienen: National Academy of Sciences of the United States of America, 1980
  • Erschienen in: Proceedings of the National Academy of Sciences of the United States of America, 77 (1980) 7, Seite 4287-4291
  • Sprache: Englisch
  • ISSN: 0027-8424
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  • Beschreibung: Nucleated bone marrow cells from normal individuals and from three patients with homozygous β+-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 β -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 β+-thalassemic cells the processing of β -globin RNA is defective. In one patient the β -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 α -globin mRNA precursor and intermediates are processed efficiently to mRNA-sized molecules in thalassemic and normal cells. The reduction in the rate of β -globin but not α -globin RNA processing accounts for the α /β globin mRNA imbalance in thalassemic erythroid cells. We discuss the possibility that the genetic lesions in β+-thalassemia are at splicing signal sites within intervening sequences of the β -globin gene.
  • Zugangsstatus: Freier Zugang