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The human gamma-globin genes form part of a 5-kb tandem duplication within the beta-globin gene cluster on chromosome 11. Despite a high degree of identity between the two genes, we show that while the upstream Ggamma-globin gene terminates transcription efficiently, termination in the Agamma gene is inefficient. This is primarily due to the different strengths of the polyA signals of the two genes; Ggamma-globin has a functionally stronger polyA signal than the Agamma gene. The probable cause of this difference in polyA efficiency characteristics lies with a number of base changes which reduce the G/U content of the GU/U-rich region of the Agamma polyA signal relative to that of Ggamma. The 3' flanking regions of the two gamma-globin genes have similar abilities to promote transcription termination. We found no evidence to suggest a cotranscriptional cleavage event, such as that seen in the human beta-globin gene, occurs in either gamma-globin 3' flank. Instead we find evidence that the 3' flank of the Ggamma-globin gene contains multiple weak pause elements which, combined with the strong polyA signal the gene possesses, are likely to cause gradual termination across the 3' flank.

Original publication

DOI

10.1128/MCB.25.8.3276-3285.2005

Type

Journal article

Journal

Mol Cell Biol

Publication Date

04/2005

Volume

25

Pages

3276 - 3285

Keywords

3' Untranslated Regions, Base Sequence, Gene Duplication, Globins, HeLa Cells, Humans, Molecular Sequence Data, Multigene Family, Poly A, Polyadenylation, RNA Processing, Post-Transcriptional, Terminator Regions, Genetic, Transcription, Genetic