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PubMed · 2775294

Abnormal processing of beta-Malay globin RNA.

J M Gonzalez-Redondo·H E Brickner·G F Atweh
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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.

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Base SequenceGene AmplificationGlobinsHeLa CellsHemoglobins, AbnormalHumansIn Vitro TechniquesRNA Processing, Post-TranscriptionalRNA, MessengerThalassemiaTransfectionJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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J M Gonzalez-Redondo, H E Brickner, G F Atweh. 1989-08-30. Abnormal processing of beta-Malay globin RNA.. https://doi.org/10.1016/0006-291x(89)92090-1

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