PolyA signals located near 5’ of genes are silenced by a general mechanism that prevents premature 3’ end processing

Guo, Jiannan (2011). PolyA signals located near 5’ of genes are silenced by a general mechanism that prevents premature 3’ end processing. University of Birmingham. Ph.D.

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Abstract

PolyA signals located at the 3’ end of eukaryotic genes drive the cleavage and polyadenylation reaction to the nascent pre-mRNA. Although these sequences are expected only at the 3’ end of genes, we found that strong polyA signals are also present within the 5’ untranslated regions (UTRs) of many Drosophila melanogaster mRNAs. Although the polyA signals in 5’ UTRs show little activity of triggering 3’ end processing in the endogenous transcripts, they are very active when placed at the 3’ end of reporter genes. We further investigated these unexpected observations and discovered that both these novel polyA signals and standard polyA signals become functionally silent when they are positioned close to transcription start sites in either Drosophila or human cells. This suggests that the transcriptional stage when the polyA signal emerges from the polymerase II (Pol II) transcription complex could determine whether a putative polyA signal is recognized as functional. The data suggest that this mechanism, which probably prevents cryptic polyA signals from causing premature transcription termination, depends on low Ser2 phosphorylation of the C-terminal domain of Pol II and inefficient recruitment of processing factors.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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