title: Abnormal RNA processing due to the exon mutation of beta E-globin gene.
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.
mesh_terms: D001483:Base Sequence; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D012323:RNA Processing, Post-Transcriptional; D012326:RNA Splicing; D013789:Thalassemia / Q000235:genetics*
chemical_list: D005914:Globins