A single-base change at a splice site in a beta 0-thalassemic gene causes abnormal RNA splicing.

Journal article

We have studied the structure and transcription of a cloned human beta-globin gene from a fetus diagnosed for beta 0 thalassemia. The sequence of the beta 0 gene differs from that of a normal beta-globin gene at positions 1 and 74 of the second intervening sequence (IVS2). The position 1 change alters the GT dinucleotide conserved at 5' splice sites, while the position 74 change is a common sequence polymorphism. When the cloned beta 0 gene is introduced into HeLa cells by use of an SV40-derived plasmid vector, two abnormally spliced cytoplasmic beta-globin RNAs are detected. The predominant RNA differs from normal beta-globin mRNA by the insertion of the first 47 nucleotides of IVS2 between exons 2 and 3. The less abundant RNA comprises the normal first exon spliced directly to the third. Analysis of nuclear RNA suggests that the beta 0 transcript is inefficiently spliced and that the removal of the two intervening sequences is coupled.

Authors: Treisman, R; Proudfoot, N; Shander, M; Maniatis, T

• Publication status: Published
• Journal: Cell
• Volume: 29
• Issue: 3
• Pages: 903-911
• Publication date: 1982-07-01
• DOI: 10.1016/0092-8674(82)90452-4
• EISSN: 1097-4172
• ISSN: 0092-8674
• Language: English
• Keywords: RNA, Messenger; Cloning, Molecular; Genes; Thalassemia; RNA Splicing; Globins; Base Sequence; Humans; Cell Nucleus; RNA Processing, Post-Transcriptional; Hela Cells; Transcription, Genetic