A Mechanistic Model for Cooperative Behavior of Co-transcribing RNA Polymerases

In fast-transcribing prokaryotic genes, such as an rrn gene in Escherichia coli, many RNA polymerases (RNAPs) transcribe the DNA simultaneously. Active elongation of RNAPs is often interrupted by pauses, which has been observed to cause RNAP traffic jams; yet some studies indicate that elongation seems to be faster in the presence of multiple RNAPs than elongation by a single RNAP. We propose that an interaction between RNAPs via the torque produced by RNAP motion on helically twisted DNA can explain this apparent paradox. We have incorporated the torque mechanism into a stochastic model and simulated transcription both with and without torque. Simulation results illustrate that the torque causes shorter pause durations and fewer collisions between polymerases. Our results suggest that the torsional interaction of RNAPs is an important mechanism in maintaining fast transcription times, and that transcription should be viewed as a cooperative group effort by multiple polymerases.Author Summary: Transcription of DNA by RNA polymerases is the first step of gene expression. It has been known that multiple RNA polymerases copying the same gene help each other to move faster, but the mechanism of this interaction is not known. We propose that the torque imposed by polymerase on helically twisted DNA and transmitted to the neighboring polymerases may play a central role in the observed cooperative behavior of polymerases. We incorporated the torque between polymerases into a basic stochastic elongation model and found that transcription times in this model match experimental data better than those of the same stochastic model without the torque effects. Using torque as the interacting mechanism of polymerases leads to significantly fewer collisions and traffic jams of polymerases. The resulting motion of polymerases resembles the motion of velocity-synchronized driverless cars on the highway.