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Control of transcription elongation by GreA determines rate of gene expression in Streptococcus pneumoniae

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.

Publication metadata

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


DOI: 10.1093/nar/gku790


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Funder referenceFunder name
Sysmo2 Grant (Noisy Strep)
UK Biotechnology and Biological Sciences Research Council
337399-PneumoCellEuropean Research Council
864.12.001Netherlands Organisation for Scientific Research (NWO-ALW VIDI)
ERC-2007-StG 202994-MTPEuropean Research Council