Interacting RNA polymerase motors on DNA track: effects of traffic congestion and intrinsic noise on RNA synthesis

TL;DR

This paper presents a theoretical model of RNA polymerase traffic on DNA, analyzing how congestion and intrinsic noise affect mRNA synthesis rates and fluctuations, with implications for understanding gene expression variability.

Contribution

It introduces a novel model incorporating steric interactions and mechano-chemical cycles of RNAPs, providing analytical and numerical insights into transcription dynamics.

Findings

RNAP traffic influences mRNA synthesis rates

Intrinsic noise depends on RNAP and reactant concentrations

Density profiles and fluctuation measures are characterized

Abstract

RNA polymerase (RNAP) is an enzyme that synthesizes a messenger RNA (mRNA) strand which is complementary to a single-stranded DNA template. From the perspective of physicists, an RNAP is a molecular motor that utilizes chemical energy input to move along the track formed by a DNA. In many circumstances, which are described in this paper, a large number of RNAPs move simultaneously along the same track; we refer to such collective movements of the RNAPs as RNAP traffic. Here we develop a theoretical model for RNAP traffic by incorporating the steric interactions between RNAPs as well as the mechano-chemical cycle of individual RNAPs during the elongation of the mRNA. By a combination of analytical and numerical techniques, we calculate the rates of mRNA synthesis and the average density profile of the RNAPs on the DNA track. We also introduce, and compute, two new measures of fluctuations in the synthesis of RNA. Analyzing these fluctuations, we show how the level of {\it intrinsic noise} in mRNA synthesis depends on the concentrations of the RNAPs as well as on those of some of the reactants and the products of the enzymatic reactions catalyzed by RNAP. We suggest appropriate experimental systems and techniques for testing our theoretical predictions.