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

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 the 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, when enriched with thymine bases, contain the signal for inducing abortive transcription, whereas certain repetitive sequence elements embedded in promoter regions constitute the signal for inducing pausing. Both signals decrease the productivity of transcription initiation. Based on solution NMR and in vitro transcription measurements, we suggest that repetitive sequence elements within the promoter DNA modulate the nonlocal base pair stability of its double-stranded form. This stability profoundly influences the reaction coordinates of the productive initiation via pausing.

The Context-Dependent Influence of Promoter Sequence Motifs on Transcription Initiation Kinetics and Regulation

“…Observations on the effects of general base composition on escape propensity have also been made. A nontemplate purine-rich ITS favors productive transcription and fast escape kinetics, whereas a T-rich ITS promotes abortive transcription and slow escape (99,184,188,189). Importantly, promoter escape can represent the rate-limiting step for some promoters (190), explained in part by ITS effects on abortive probabilities, escape kinetics, and pausing.…”

RNA Polymerase and Transcription Mechanisms: The Forefront of Physicochemical Studies of Chemical Reactions

“…In the sigma-70 promoter of E. coli , several functional motifs have been proposed, a −10 motif and a −35 motif, for example [ 2 , 3 , 4 , 5 , 6 , 7 ]. Imashimizu et al combined statistical mechanics with high-throughput sequencing to characterize abortive transcription and pausing during transcription initiation [ 8 ].…”