Density- and elongation speed-dependent error correction in RNA polymerization

TL;DR

This paper develops an exact stochastic model of RNA polymerase backtracking during transcription, incorporating interactions with trailing polymerases to better understand error correction mechanisms.

Contribution

It introduces a novel analytic model that explicitly accounts for interactions between backtracking and trailing RNAPs, improving understanding of error correction during transcription.

Findings

Derived exact solutions for RNAP backtracking dynamics.

Quantified how trailing RNAPs influence error correction probabilities.

Provided methods to compute mean error correction times.

Abstract

Backtracking of RNA polymerase (RNAP) is an important pausing mechanism during DNA transcription that is part of the error correction process that enhances transcription fidelity. We model the backtracking mechanism of RNA polymerase, which usually happens when the polymerase tries to incorporate a mismatched nucleotide triphosphate. Previous models have made simplifying assumptions such as neglecting the trailing polymerase behind the backtracking polymerase or assuming that the trailing polymerase is stationary. We derive exact analytic solutions of a stochastic model that includes locally interacting RNAPs by explicitly showing how a trailing RNAP influences the probability that an error is corrected or incorporated by the leading backtracking RNAP. We also provide two related methods for computing the mean times to error correction or incorporation given an initial local RNAP configuration.