A mechanistic model for +1 frameshifts in eubacteria

TL;DR

This paper models how translational speed influences +1 frameshifts in bacterial protein synthesis, using signal processing and control theory to identify mechanisms and regulatory signals involved.

Contribution

It introduces a mechanistic model linking free energy signals and tRNA abundance to programmed frameshifts in bacteria, integrating signal analysis with biological regulation.

Findings

Sinusoidal free energy patterns correlate with frameshift sites

Signal phase helps locate programmed +1 frameshifts

Displacement model explains frameshift mechanism based on signal content

Abstract

This work applies the methods of signal processing and the concepts of control system design to model the maintenance and modulation of reading frame in the process of protein synthesis. The model shows how translational speed can modulate translational accuracy to accomplish programmed +1 frameshifts and could have implications for the regulation of translational efficiency. A series of free energy estimates were calculated from the ribosome's interaction with mRNA sequences during the process of translation elongation in eubacteria. A sinusoidal pattern of roughly constant phase was detected in these free energy signals. Signal phase was identified as a useful parameter for locating programmed +1 frameshifts encoded in bacterial genes for release factor 2. A displacement model was developed that captures the mechanism of frameshift based on the information content of the signal parameters and the relative abundance of tRNA in the bacterial cell. Results are presented using experimentally verified frameshift genes across eubacteria.