Long-Range Supercoiling-Mediated RNA Polymerase Cooperation in Transcription

Abstract

It is widely believed that DNA supercoiling plays an important role in the regulation of transcriptional dynamics. Recent studies show that it could affect transcription not only through the buildup and relaxation of torsional strain on DNA strands but also via effective long-range supercoiling-mediated interactions between RNA polymerase (RNAP) molecules. Here, we present a theoretical study that quantitatively analyzes the effect of long-range RNAP cooperation in transcription dynamics. Our minimal chemical-kinetic model assumes that one or two RNAP molecules can simultaneously participate in the transcription, and it takes into account their binding to and dissociation from DNA. It also explicitly accounts for competition between the supercoiling buildup that reduces the RNA elongation speed and gyrase binding that rescues the RNA synthesis. The full analytical solution of the model accompanied by Monte Carlo computer simulations predicts that the system should exhibit transcriptional bursting dynamics, in agreement with experimental observations. The analysis also revealed that when there are two polymerases participating in the elongation rather than one, the transcription process becomes much more efficient since the level of stochastic noise decreases while more RNA transcripts are produced. Our theoretical investigation clarifies molecular aspects of the supercoiling-mediated RNAP cooperativity during transcription.

Interaction Between Transcribing RNA Polymerase and Topoisomerase I Prevents R-loop Formation in E. coli

“…This can reflect activation of EcTopoI by extensive torsional stress generated by individual RNAP molecules expected in LETUs. Conversely, in HETUs, convoys of RNAP molecules should mutually annihilate positive and negative supercoils (Kim et al, 2019;Alena and Kolomeisky, 2021). Second, no activity of MsmTopoI was detected in extended regions upstream of TUs, while EcTopoI activity in these regions is significantly increased, again illustrating the proposed "open" and "closed" variants of the twin-domain model.…”

An Accurate and Stable Filtered Explicit Scheme for Biopolymerization Processes in the Presence of Perturbations

“…As numerically tested decreasing the time step by about 20% to ∆t = 2 5 ∆x, the oscillations disappear resulting in a smooth surface. Similarly, when using a double time filter with the time step ∆t = 2 7 ∆x based on the CFL condition shown in Proposition 4.2, we experience the presence of small oscillations on the top surface area. Reducing the time step to ∆t = 0.22∆x by about 23%, the surface becomes smooth, see Figure 3.…”

“…Protein synthesis is a complex biopolymerization process requiring an immense amount of cellular energy. Transcription and translation are two key stages of protein synthesis, and a full understanding and model characterization of these mechanisms is an active area of research for experimentalists and modelers [1,2,3,4]. Transcription involves the transfer of genetic information from DNA to several types of RNA including messenger mRNA, transfer RNA, ribosomal RNA and others.…”

“…1 128 and ∆t =2 5 ∆x. The analytic values are given for comparison.Motivated by the LWR traffic flow model, this work gives the derivation of a simple continuum model for RNAPs transcribing a gene on a DNA strand.…”

A spatially resolved stochastic model reveals the role of supercoiling in transcription regulation

“…Although supercoiling is proposed to mediate the communication between multiple RNAP molecules and multiple genes, it is not clear how supercoiling dynamics lead to changes in transcription activities quantitatively and how these changes are dependent on the mechanical properties of DNA and the transcription kinetics of RNAP. Several models [20,21,22,23,24,25,26,27,28] have been established to explore the role of supercoiling in transcription regulation. However, none of these models fully captured the complex interactions between transcription and supercoiling.…”