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Factor-independent transcription pausing caused by recognition of the RNA-DNA hybrid sequence

Lookup NU author(s): Dr Aleksandra Bochkareva, Dr Yulia Yuzenkova, Professor Nikolay ZenkinORCiD

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Abstract

Pausing of transcription is an important step of regulation of gene expression in bacteria and eukaryotes. Here we uncover a factor-independent mechanism of transcription pausing, which is determined by the ability of the elongating RNA polymerase to recognize the sequence of the RNA-DNA hybrid. We show that, independently of thermodynamic stability of the elongation complex, RNA polymerase directly 'senses' the shape and/or identity of base pairs of the RNA-DNA hybrid. Recognition of the RNA-DNA hybrid sequence delays translocation by RNA polymerase, and thus slows down the nucleotide addition cycle through 'in pathway' mechanism. We show that this phenomenon is conserved among bacterial and eukaryotic RNA polymerases, and is involved in regulatory pauses, such as a pause regulating the production of virulence factors in some bacteria and a pause regulating transcription/replication of HIV-1. The results indicate that recognition of RNA-DNA hybrid sequence by multi-subunit RNA polymerases is involved in transcription regulation and may determine the overall rate of transcription elongation. The EMBO Journal (2012) 31, 630-639. doi: 10.1038/emboj.2011.432; Published online 29 November 2011

Publication metadata

Author(s): Bochkareva A, Yuzenkova Y, Tadigotla VR, Zenkin N

Publication type: Article

Publication status: Published

Journal: EMBO Journal

Year: 2012

Volume: 31

Issue: 3

Pages: 630-639

Print publication date: 29/11/2011

Date deposited: 10/06/2013

ISSN (print): 0261-4189

ISSN (electronic): 1460-2075

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/emboj.2011.432

DOI: 10.1038/emboj.2011.432

PubMed id: PMC3273390

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