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Alpha‐thalassaemia caused by a poly(A) site mutation reveals that transcriptional termination is linked to 3′ end processing in the human alpha 2 globin gene.

We have investigated the process of transcriptional termination in the duplicated human alpha globin genes which lie 4 kb apart on chromosome 16. In the human erythroleukemic cell line, K562, which expresses high levels of alpha globin, nuclear run‐off experiments suggest that termination occurs within a region of 600 bp past the poly(A) site of both alpha 1 and alpha 2 globin genes. However, a thalassaemic alpha 2 globin gene with a non‐functional poly(A) site AAUAAG, when transfected into HeLa cells, not only fails to 3′ end process but also fails to terminate transcription. Studies on both steady‐state RNA and nuclear run‐off analysis of the primary transcripts show that transcription of the mutant alpha 2 globin gene reads through into the intergenic sequence past the normal termination site. These results demonstrate that transcriptional termination and 3′ end processing of mRNA are coupled events for the alpha 2 globin gene.