Residence Time Analysis of RNA Polymerase Transcription Dynamics: A Bayesian Sticky HMM Approach

Published: July 29, 2020, 12:01 a.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.28.132373v1?rss=1 Authors: Kilic, Z., Sgouralis, I., Presse, S. Abstract: The time spent by a single RNA polymerase (RNAP) at specific locations along the DNA, termed "residence time", reports on the initiation, elongation and termination stages of transcription. At the single molecule level, this information can be obtained from dual ultra-stable optical trapping experiments, revealing a transcriptional elongation of RNAP interspersed with residence times of variable duration. Successfully discriminating between long and short residence times was used by previous approaches to learn about RNAP's transcription elongation dynamics. Here, we propose an approach based on the Bayesian sticky hidden Markov models that treats all residence times, for an E. Coli RNAP, on an equal footing without a priori discriminating between long and short residence times. In addition, our method has two additional advantages, we provide: full distributions around key point statistics; and directly treat the sequence-dependence of RNAP's elongation rate. By applying our approach to experimental data, we find: no emergent separation between long and short residence times warranted by the data; force dependent average residence time transcription elongation dynamics; limited effects of GreB on average backtracking durations and counts; and a slight drop in the average residence time as a function of applied force in RNaseA's presence. Copy rights belong to original authors. Visit the link for more info