Pausing controls branching between productive and non-productive pathways during initial transcription in bacteria

Dulin D, Bauer DLV, Malinen AM, Bakermans JJW, Kaller M, Morichaud Z, Petushkov I, Depken M, Brodolin K, Kulbachinskiy A, Kapanidis AN (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 9

Journal Issue: 1

DOI: 10.1038/s41467-018-03902-9

Abstract

Transcription in bacteria is controlled by multiple molecular mechanisms that precisely regulate gene expression. It has been recently shown that initial RNA synthesis by the bacterial RNA polymerase (RNAP) is interrupted by pauses; however, the pausing determinants and the relationship of pausing with productive and abortive RNA synthesis remain poorly understood. Using single-molecule FRET and biochemical analysis, here we show that the pause encountered by RNAP after the synthesis of a 6-nt RNA (ITC6) renders the promoter escape strongly dependent on the NTP concentration. Mechanistically, the paused ITC6 acts as a checkpoint that directs RNAP to one of three competing pathways: productive transcription, abortive RNA release, or a new unscrunching/scrunching pathway. The cyclic unscrunching/scrunching of the promoter generates a long-lived, RNA-bound paused state; the abortive RNA release and DNA unscrunching are thus not as tightly linked as previously thought. Finally, our new model couples the pausing with the abortive and productive outcomes of initial transcription.

Authors with CRIS profile

David Dulin Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe 2 Prof. Dr. Dulin

Involved external institutions

University of Oxford GB United Kingdom (GB) Russian Academy of Sciences / Росси́йская акаде́мия нау́к (RAS) RU Russian Federation (RU) University of Montpellier / Université Montpellier FR France (FR) Delft University of Technology (TU Delft) NL Netherlands (NL)

How to cite

APA:

Dulin, D., Bauer, D.L.V., Malinen, A.M., Bakermans, J.J.W., Kaller, M., Morichaud, Z.,... Kapanidis, A.N. (2018). Pausing controls branching between productive and non-productive pathways during initial transcription in bacteria. Nature Communications, 9(1). https://dx.doi.org/10.1038/s41467-018-03902-9

MLA:

Dulin, David, et al. "Pausing controls branching between productive and non-productive pathways during initial transcription in bacteria." Nature Communications 9.1 (2018).

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