Mechanical Interplay Between Transcription Elongation and DNA Supercoiling

During transcription elongation, an RNA polymerase II (RNAP) negatively supercoils (untwists) the DNA upstream and positively supercoils (overtwists) the DNA downstream [1]. The resultant torsional stress in the DNA [2, 3], if not relaxed quickly, can interfere with the RNAP movement [4]. Here, we present a theoretical model incorporating coupling between RNAP translocation and the DNA torsional response which predicts the RNAP velocity profile under DNA stretching and twisting. Using stochastic simulations, we demonstrate long-distance cooperation between multiple RNAPs and show that inhibiting transcription initiation can slow down the already recruited RNAPs, in agreement with recent experimental findings [5]. We predict that the average transcription elongation rate varies non-monotonically with the rate of transcription initiation. We further show that while RNAPs transcribing neighboring genes oriented in tandem can cooperate, those transcribing genes in divergent or convergent orientations can act antagonistically, and that such behavior holds over a large range of intergenic separations. Our model makes testable predictions, providing important insights into the mechanical control of a key cellular process.