Abnormal RNA processing due to the exon mutation of βE-globin gene
- 1 December 1982
- journal article
- Published by Springer Nature in Nature
- Vol. 300 (5894) , 768-769
- https://doi.org/10.1038/300768a0
Abstract
As is typical of all beta-thalassaemias, the erythroid cells of individuals with the variant haemoglobin E (alpha 2 beta 2(26Glu leads to Lys)) exhibit a quantitative deficiency in their content of beta-globin (in this case beta E-globin) and its messenger RNA2,3. To determine the molecular basis of this phenotype, we have investigated the structure and expression of cloned beta E-globin genes. We report here that the complete nucleotide sequence of a beta E-gene revealed the expected GAG leads to AAG change in codon 26 but no other mutations. Expression of beta E-globin genes introduced into HeLa cells revealed two abnormalities of RNA processing: slow excision of intervening sequence-1 (IVS-1) and alternative splicing into exon-1 at a cryptic donor sequence within which the codon 26 nucleotide substitution resides. These results demonstrate a disturbance in the expression of the beta E-gene attributable solely to the exon mutation-a novel mechanism for gene dysfunction.Keywords
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