Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Control of Transcription Initiation by Biased Thermal Fluctuations on Repetitive Genomic Sequences

Version 1 : Received: 23 August 2020 / Approved: 25 August 2020 / Online: 25 August 2020 (11:28:21 CEST)

A peer-reviewed article of this Preprint also exists.

Imashimizu, M.; Tokunaga, Y.; Afek, A.; Takahashi, H.; Shimamoto, N.; Lukatsky, D.B. Control of Transcription Initiation by Biased Thermal Fluctuations on Repetitive Genomic Sequences. Biomolecules 2020, 10, 1299. Imashimizu, M.; Tokunaga, Y.; Afek, A.; Takahashi, H.; Shimamoto, N.; Lukatsky, D.B. Control of Transcription Initiation by Biased Thermal Fluctuations on Repetitive Genomic Sequences. Biomolecules 2020, 10, 1299.

Abstract

In the process of transcription initiation by RNA polymerase, promoter DNA sequences affect multiple reaction pathways determining the productivity of transcription. However, the question of how the molecular mechanism of transcription initiation depends on sequence properties of promoter DNA remains poorly understood. Here, combining the statistical mechanical approach with high-throughput sequencing results, we characterize abortive transcription and pausing during transcription initiation by Escherichia coli RNA polymerase at a genome-wide level. Our results suggest that initially transcribed sequences enriched with thymine bases represent the signal inducing abortive transcription. On the other hand, certain repetitive sequence elements broadly embedded in promoter regions constitute the signal inducing pausing. Both signals decrease the productivity of transcription initiation. Based on solution NMR and in vitro transcription measurements, we also suggest that repetitive sequence elements of promoter DNA modulate the rigidity of its double-stranded form, which profoundly influences the reaction coordinates of the productive initiation via pausing.

Keywords

promoter sequences; repetitive sequences; pausing; abortive initiation; RNA polymerase; dsDNA rigidity

Subject

Biology and Life Sciences, Biophysics

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