Mechanical Control of Transcriptional Elongation by DNA Supercoiling

Transcriptional elongation by an RNA polymerase II (RNAP) positively supercoils (overtwists) the downstream DNA and negatively supercoils (untwists) the upstream DNA. The resultant DNA torsional stress, if not relaxed quickly, can hinder transcriptional elongation. Recent experiments have shown that multiple RNAPs transcribing a gene may cooperate by neutralizing the supercoils generated by their neighbors. Here, we describe a theoretical model that couples RNAP motion and DNA torsional response, and use the model to predict the RNAP velocity on stretched and / or twisted DNA. Using stochastic simulations, we demonstrate long-range cooperation between multiple RNAPs transcribing a gene, and find that inhibiting transcription initiation can slow down the RNAPs already recruited. Further, we investigate the coupling between RNAPs transcribing genes in different orientations— tandem, divergent, and convergent— and report that our model predictions agree with experimental observations. Our model thus provides key insights into how DNA supercoiling can regulate transcriptional elongation and makes new predictions that can be tested in future experiments.