Stochasticity and traffic jams in the transcription of ribosomal RNA: Intriguing role of termination and antitermination

TL;DR

This study models how stochastic pausing and termination events of RNA polymerases affect high-rate rRNA transcription in bacteria, highlighting the importance of antitermination complexes and Rho factor in maintaining efficient transcription under dense traffic conditions.

Contribution

The paper introduces a stochastic model integrating experimental data to elucidate the roles of pausing, termination, and antitermination in bacterial rRNA transcription, revealing new insights into traffic jam mitigation.

Findings

RNAP pausing can cause severe traffic jams limiting transcription.

Antitermination complexes suppress pauses, essential for fast growth.

Rho factor can remove non-antiterminated RNAPs, restoring transcription.

Abstract

In fast growing bacteria, ribosomal RNA (rRNA) is required to be transcribed at very high rates to sustain the high cellular demand on ribosome synthesis. This results in dense traffic of RNA polymerases (RNAP). We developed a stochastic model, integrating results of single-molecule and quantitative in vivo studies of E. coli, to evaluate the quantitative effect of pausing, termination, and antitermination on rRNA transcription. Our calculations reveal that in dense RNAP traffic, spontaneous pausing of RNAP can lead to severe "traffic jams", as manifested in the broad distribution of inter-RNAP distances and can be a major factor limiting transcription and hence growth. Our results suggest the suppression of these pauses by the ribosomal antitermination complex to be essential at fast growth. Moreover, unsuppressed pausing by even a few non-antiterminated RNAPs can already reduce transcription drastically under dense traffic. However, the termination factor Rho can remove the non-antiterminated RNAPs and restore fast transcription. The results thus suggest an intriguing role by Rho to enhance rather than attenuate rRNA transcription.