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Biomedical subjects

Michael J Dye

Publications and source records attributed to Michael J Dye.

3 recordsLinked to original sources

Exon tethering in transcription by RNA polymerase II.

There is an emerging consensus that RNA polymerase II (RNA Pol II) transcription and pre-mRNA processing are tightly coupled events. We show here that exons flanking an intron that has been engineered to be co-transcriptionally cleaved are accurately and efficiently spliced together. These data underline the close coupling of processes in the initial stages of protein-encoding gene expression and provide evidence for a molecular tether connecting emergent splice sites in the pre-mRNA to transcribing RNA Pol II. This observation suggests that for some genes a continuous intron transcript is not required for pre-mRNA splicing in vivo.

Animals↗

Strong polyadenylation and weak pausing combine to cause efficient termination of transcription in the human Ggamma-globin gene.

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.

3' Untranslated Regions↗

Integrating mRNA processing with transcription.

The messenger RNA processing reactions of capping, splicing, and polyadenylation occur cotranscriptionally. They not only influence one another's efficiency and specificity, but are also coordinated by transcription. The phosphorylated CTD of RNA polymerase II provides key molecular contacts with these mRNA processing reactions throughout transcriptional elongation and termination.

Histones↗