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

Guo, Jiannan (2011)
Ph.D. thesis, University of Birmingham.

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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:Ph.D. thesis.
Supervisor(s):Brogna, Saverio
School/Faculty:Colleges (2008 onwards) > College of Life & Environmental Sciences
Department:School of Biosciences
Subjects:Q Science (General)
QR Microbiology
Institution:University of Birmingham
ID Code:1297
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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