Abnormal RNA processing due to the exon mutation of βE- globin gene

Stuart H. Orkin, Haig H. Kazazian, Stylianos E. Antonarakis, Harry Ostrer, Sabra C. Goff, Julianne P. Sexton

Research output: Contribution to journalArticle

205 Citations (Scopus)

Abstract

As is typical of all β-thalassaemias1, the erythroid cells of individuals with the variant haemoglobin E (α2β 226Glu→Lys) exhibit a quantitative deficiency in their content of β-globin (in this case βE-globin) and its messenger RNA2,3. To determine the molecular basis of this phenotype, we have investigated the structure and expression of cloned βE-globin genes. We report here that the complete nucleotide sequence of a βE-gene revealed the expected GAG → AAG change in codon 26 but no other mutations. Expression of βE- 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 βE-gene attributable solely to the exon mutation - A novel mechanism for gene dysfunction.

Original languageEnglish (US)
Pages (from-to)768-769
Number of pages2
JournalNature
Volume300
Issue number5894
DOIs
StatePublished - 1982
Externally publishedYes

Fingerprint

Globins
Exons
RNA
Mutation
Codon
Genes
Hemoglobin E
Erythroid Cells
Alternative Splicing
HeLa Cells
Introns
Nucleotides
Phenotype
Gene Expression

ASJC Scopus subject areas

  • General

Cite this

Orkin, S. H., Kazazian, H. H., Antonarakis, S. E., Ostrer, H., Goff, S. C., & Sexton, J. P. (1982). Abnormal RNA processing due to the exon mutation of βE- globin gene. Nature, 300(5894), 768-769. https://doi.org/10.1038/300768a0

Abnormal RNA processing due to the exon mutation of βE- globin gene. / Orkin, Stuart H.; Kazazian, Haig H.; Antonarakis, Stylianos E.; Ostrer, Harry; Goff, Sabra C.; Sexton, Julianne P.

In: Nature, Vol. 300, No. 5894, 1982, p. 768-769.

Research output: Contribution to journalArticle

Orkin, SH, Kazazian, HH, Antonarakis, SE, Ostrer, H, Goff, SC & Sexton, JP 1982, 'Abnormal RNA processing due to the exon mutation of βE- globin gene', Nature, vol. 300, no. 5894, pp. 768-769. https://doi.org/10.1038/300768a0
Orkin SH, Kazazian HH, Antonarakis SE, Ostrer H, Goff SC, Sexton JP. Abnormal RNA processing due to the exon mutation of βE- globin gene. Nature. 1982;300(5894):768-769. https://doi.org/10.1038/300768a0
Orkin, Stuart H. ; Kazazian, Haig H. ; Antonarakis, Stylianos E. ; Ostrer, Harry ; Goff, Sabra C. ; Sexton, Julianne P. / Abnormal RNA processing due to the exon mutation of βE- globin gene. In: Nature. 1982 ; Vol. 300, No. 5894. pp. 768-769.
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