Abnormal processing of beta-Malay globin RNA.

Abstract

Hemoglobin Malay (alpha 2 beta 2 19 Asn----Ser) has been observed in a few Malaysian patients with thalassemia intermedia. The beta Malay substitution increases the homology of the cryptic splice site at codons 17/18/19 of the beta-globin gene to the donor consensus splice sequence, suggesting that the beta-thalassemia associated with this mutation may be due to the generation of a new splice site. To test this hypothesis, we constructed a hybrid gene where we replaced part of a normal beta-globin gene with a PCR amplified region of the beta Malay gene. The expression of this mutant gene was studied in a heterologous transient expression system. The data show that nearly 25% of globin mRNA produced by this gene is abnormally spliced at the new splice site, providing a molecular mechanism for the beta-thalassemia associated with the mutation.

• Authors: J M Gonzalez-Redondo, H E Brickner, G F Atweh
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 163 Issue 1 Pg. 8-13 (Aug 30 1989) ISSN: 0006-291X [Print] United States
• PMID: 2775294 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Hemoglobins, Abnormal
• RNA, Messenger
• Globins

Topics

• Base Sequence
• Gene Amplification
• Globins (genetics)
• HeLa Cells
• Hemoglobins, Abnormal (genetics)
• Humans
• In Vitro Techniques
• RNA Processing, Post-Transcriptional
• RNA, Messenger (genetics)
• Thalassemia (genetics)
• Transfection