Folding Kinetics of Riboswitch Transcriptional Terminators and Sequesterers

TL;DR

This study uses kinetic Monte Carlo simulations to analyze how riboswitches fold during transcription, revealing differences in folding efficiency between terminators and sequesterers, and implications for their regulatory functions.

Contribution

It introduces a computational model to compare folding kinetics of riboswitch elements, highlighting natural selection for terminator efficiency and functional robustness of sequesterers.

Findings

Terminators fold more efficiently than sequesterers during transcription.

Sequesterers can function despite significant misfolding.

Natural selection favors high folding efficiency in terminator sequences.

Abstract

To function as gene regulatory elements in response to environmental signals, riboswitches must adopt specific secondary structures on appropriate time scales. We employ kinetic Monte Carlo simulation to model the time-dependent folding during transcription of TPP riboswitch expression platforms. According to our simulations, riboswitch transcriptional terminators, which must adopt a specific hairpin configuration by the time they have been transcribed, fold with higher efficiency than Shine-Dalgarno sequesterers, whose proper structure is required only at the time of ribosomal binding. Our findings suggest both that riboswitch transcriptional terminator sequences have been naturally selected for high folding efficiency, and that sequesterers can maintain their function even in the presence of significant misfolding.