title: Strong polyadenylation and weak pausing combine to cause efficient termination of transcription in the human Ggamma-globin gene.
abstract: 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.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Plant
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Dye
authors.forename: Celina
authors.initials: C
authors.lastname: Lafaille
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Proudfoot
mesh_terms: D020413:3' Untranslated Regions / Q000378:metabolism*; D001483:Base Sequence; D020440:Gene Duplication; D005914:Globins / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D011061:Poly A / Q000235:genetics; D026723:Polyadenylation; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology*; D013728:Terminator Regions, Genetic; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D020413:3' Untranslated Regions; D011061:Poly A; D005914:Globins