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

• Main Authors: Andreev, D.E (Author), Baranov, P.V (Author), Milogorodskii, A. (Author), Rachinskii, D. (Author)
• Format: Article
• Language: English
• Published: Oxford University Press 2021
• Subjects: Asymptotic of stationary solution; Asymptotics; Asymptotics of stationary solution; Deterministic modeling; Macromolecules; Modified tasep model; Mrna translation regulation; open reading frame; Open reading frame; Open Reading Frames; Ordinary differential equation model; Ordinary differential equation models; Ordinary differential equations; Stationary solutions; Stress resistance; Translation regulation
• Online Access: View Fulltext in Publisher

 Totally asymmetric simple exclusion process (TASEP) modelling 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. © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.