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

Abstract

As is typical of all β-thalassaemias1, the erythroid cells of individuals with the variant haemoglobin E (α2β226Glu→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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Weatherall, D. J. & Clegg, J. B. Cell 29, 7–9 (1982).

  2. 2

    Traeger, J., Wood, W. G., Clegg, J. B. & Weatherall, D. J. Nature 288, 497–499 (1980).

  3. 3

    Benz, E. J. Jr et al. J. clin. Invest. 68, 118–126 (1981).

  4. 4

    Antonarakis, S. E. et al. Proc. natn. Acad. Sci. U.S.A. 79, 6608–6611 (1982).

  5. 5

    Maxam, A. & Gilbert, W. Meth. Enzym. 65, 499–560 (1980).

  6. 6

    Treisman, R., Proudfoot, N. J., Shander, M. & Maniatis, T. Cell 29, 903–911 (1982).

  7. 7

    Banerji, J., Rusconi, S. & Schaffner, W. Cell 27, 299–308 (1981).

  8. 8

    Busslinger, M., Moschonas, N. & Flavell, R. A. Cell 27, 289–308 (1981).

  9. 9

    Thomas, P. Proc. natn. Acad. Sci. U.S.A. 77, 5201–5205 (1980).

  10. 10

    Weaver, R. F. & Weissmann, C. Nucleic Acids Res. 7, 1175–1193 (1979).

  11. 11

    Breathnach, R. & Chambon, P. A. Rev. Biochem. 50, 349–383 (1981).

  12. 12

    Mount, S. M. Nucleic Acids Res. 10, 459–472 (1982).

  13. 13

    Felber, B. K., Orkin, S. H. & Hamer, D. H. Cell 29, 895–902 (1982).

  14. 14

    Fukumaki, Y. et al. Cell 28, 585–593 (1982).

  15. 15

    Traeger, J., Winichagoon, P. & Wood, W. H. J. clin. Invest. 69, 1050–1053 (1982).

  16. 16

    Orkin, S. H. et al. Nature 296, 627–631 (1982).

  17. 17

    Favaloro, J., Treisman, R. & Kamen, R. Meth. Enzym. 68, 718–749 (1980).

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Orkin, S., Kazazian, H., Antonarakis, S. et al. Abnormal RNA processing due to the exon mutation of βE-globin gene. Nature 300, 768–769 (1982). https://doi.org/10.1038/300768a0

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.