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Lookup NU author(s): Dr Yulia Yuzenkova, Dr Pamela Gamba, Professor Nikolay ZenkinORCiD, Dr Jan-Willem Veening
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Transcription by RNA polymerase may be interrupted by pauses caused by backtracking or misincorporation that can be resolved by the conserved bacterial Gre-factors. However, the consequences of such pausing in the living cell remain obscure. Here, we developed molecular biology and transcriptome sequencing tools in the human pathogen Streptococcus pneumoniae and provide evidence that transcription elongation is rate-limiting on highly expressed genes. Our results suggest that transcription elongation may be a highly regulated step of gene expression in S. pneumoniae. Regulation is accomplished via long-living elongation pauses and their resolution by elongation factor GreA. Interestingly, mathematical modeling indicates that long-living pauses cause queuing of RNA polymerases, which results in 'transcription traffic jams' on the gene and thus blocks its expression. Together, our results suggest that long-living pauses and RNA polymerase queues caused by them are a major problem on highly expressed genes and are detrimental for cell viability. The major and possibly sole function of GreA in S. pneumoniae is to prevent formation of backtracked elongation complexes.
Author(s): Yuzenkova Y, Gamba P, Herber M, Attaiech L, Shafeeq S, Kuipers OP, Klumpp S, Zenkin N, Veening JW
Publication type: Article
Publication status: Published
Journal: Nucleic Acids Research
Year: 2014
Volume: 42
Issue: 17
Pages: 10987-10999
Print publication date: 29/09/2014
Online publication date: 04/09/2014
Acceptance date: 20/08/2014
Date deposited: 16/02/2015
ISSN (print): 0305-1048
ISSN (electronic): 1362-4962
Publisher: Oxford University Press
URL: http://dx.doi.org/10.1093/nar/gku790
DOI: 10.1093/nar/gku790
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