When push comes to shove - RNA polymerase and DNA-bound protein roadblocks

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dc.contributor.authorHao, N.
dc.contributor.authorDonnelly, A.J.
dc.contributor.authorDodd, I.B.
dc.contributor.authorShearwin, K.E.
dc.date.issued2023
dc.description.abstractIn recent years, transcriptional roadblocking has emerged as a crucial regulatory mechanism in gene expression, whereby other DNA-bound obstacles can block the progression of transcribing RNA polymerase (RNAP), leading to RNAP pausing and ultimately dissociation from the DNA template. In this review, we discuss the mechanisms by which transcriptional roadblocks can impede RNAP progression, as well as how RNAP can overcome these obstacles to continue transcription. We examine different DNA-binding proteins involved in transcriptional roadblocking and their biophysical properties that determine their effectiveness in blocking RNAP progression. The catalytically dead CRISPR-Cas (dCas) protein is used as an example of an engineered programmable roadblock, and the current literature in understanding the polarity of dCas roadblocking is also discussed. Finally, we delve into a stochastic model of transcriptional roadblocking and highlight the importance of transcription factor binding kinetics and its resistance to dislodgement by an elongating RNAP in determining the strength of a roadblock.
dc.description.statementofresponsibilityNan Hao, Alana J. Donnelly, Ian B. Dodd, Keith E. Shearwin
dc.identifier.citationBiophysical Reviews, 2023; 15(3):355-366
dc.identifier.doi10.1007/s12551-023-01064-7
dc.identifier.issn1867-2450
dc.identifier.issn1867-2469
dc.identifier.orcidHao, N. [0000-0001-5836-3507]
dc.identifier.orcidDodd, I.B. [0000-0003-2969-6841]
dc.identifier.orcidShearwin, K.E. [0000-0002-7736-2742]
dc.identifier.urihttps://hdl.handle.net/2440/139620
dc.language.isoen
dc.publisherSpringer Science and Business Media LLC
dc.relation.granthttp://purl.org/au-research/grants/arc/DP160101450
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
dc.source.urihttps://doi.org/10.1007/s12551-023-01064-7
dc.subjectRNA polymerase, Transcriptional roadblocking, Transcriptional interference, DNA binding kinetics, CRISPR
dc.titleWhen push comes to shove - RNA polymerase and DNA-bound protein roadblocks
dc.typeJournal article
pubs.publication-statusPublished

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