A deterministic model for non-monotone relationship between translation of upstream and downstream open reading frames

TL;DR

This paper introduces a deterministic model that explains the non-monotone relationship between upstream and downstream translation flows, providing insights into uORF-mediated translation regulation during stress responses.

Contribution

It presents a new phenomenological deterministic model approximating TASEP, establishing stationary solutions and explicit relations for translation flow dynamics.

Findings

The model predicts non-monotone flow relations under certain conditions.

Stationary solutions with decreasing density along uORFs are established.

Numerical comparisons validate the deterministic model against TASEP simulations.

Abstract

TASEP modeling was shown to offer a parsimonious explanation for the experimentally confirmed ability of a single upstream Open Reading Frames (uORFs) to upregulate downstream translation during the integrated stress response. As revealed by numerical simulations, the model predicts that reducing the density of scanning ribosomes upstream of certain uORFs increases the flow of ribosomes downstream. To gain a better insight into the mechanism which ensures the non-monotone relation between the upstream and downstream flows, in this work, we propose a phenomenological deterministic model approximating the TASEP model of the translation process. We establish the existence of a stationary solution featuring the decreasing density along the uORF for the deterministic model. Further, we find an explicit non-monotone relation between the upstream ribosome density and the downstream flow for the stationary solution in the limit of increasing uORF length and increasingly leaky initiation. The stationary distribution of the TASEP model, the stationary solution of the deterministic model and the explicit limit are compared numerically.