Slip of grip of a molecular motor on a crowded track: Modeling shift of reading frame of ribosome on RNA template

TL;DR

This paper presents a stochastic model for ribosomal frameshifting during protein synthesis, highlighting how ribosome density influences the frequency of programmed -1 frameshift events on mRNA.

Contribution

It introduces a novel model that incorporates ribosome density as a key regulator of programmed frameshift, expanding understanding beyond traditional factors.

Findings

Ribosome density significantly affects frameshift frequency.

Monte Carlo simulations validate the analytical model.

Density regulation offers new insights into translation control.

Abstract

We develop a stochastic model for the programmed frameshift of ribosomes synthesizing a protein while moving along a mRNA template. Normally the reading frame of a ribosome decodes successive triplets of nucleotides on the mRNA in a step-by-step manner. We focus on the programmed shift of the ribosomal reading frame, forward or backward, by only one nucleotide which results in a fusion protein; it occurs when a ribosome temporarily loses its grip to its mRNA track. Special "slippery" sequences of nucleotides and also downstream secondary structures of the mRNA strand are believed to play key roles in programmed frameshift. Here we explore the role of an hitherto neglected parameter in regulating -1 programmed frameshift. Specifically, we demonstrate that the frameshift frequency can be strongly regulated also by the density of the ribosomes, all of which are engaged in simultaneous translation of the same mRNA, at and around the slippery sequence. Monte Carlo simulations support the analytical predictions obtained from a mean-field analysis of the stochastic dynamics.