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Updated: Oct 15, 2025
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De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
Published on: February 18, 2022
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A deterministic model for non-monotone relationship between translation of upstream and downstream open reading
D E Andreev1, P V Baranov2, A Milogorodskii1
1Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow, 119991, Russian Federation, and Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia.
Mathematical Medicine and Biology : a Journal of the IMA
|October 31, 2021
Summary
A new deterministic model explains how upstream open reading frames (uORFs) regulate gene translation. Reducing ribosome density upstream of uORFs enhances downstream translation flow, revealing a non-monotone relationship crucial for gene expression control.
Area of Science:
- Molecular Biology
- Biophysics
- Computational Biology
Background:
- Single upstream open reading frames (uORFs) are known to upregulate downstream translation during the integrated stress response.
- The Totally Asymmetric Simple Exclusion Process (TASEP) model provides a framework for understanding ribosome dynamics and translation regulation.
Purpose of the Study:
- To develop a phenomenological deterministic model that approximates the TASEP model for translation processes.
- To gain deeper insight into the mechanism behind the non-monotone relationship between upstream and downstream ribosome flow.
Main Methods:
- Numerical simulations of the TASEP model.
- Development and analysis of a deterministic model approximating TASEP.
- Derivation of an explicit non-monotone relationship in a limiting case.
Main Results:
- The deterministic model establishes a stationary solution with decreasing ribosome density along the uORF.
- An explicit non-monotone relationship between upstream ribosome density and downstream flow was found in the limit of long uORFs and leaky initiation.
- Numerical comparison of the TASEP stationary distribution, deterministic model solution, and the explicit limit.
Conclusions:
- The deterministic model successfully captures key aspects of ribosome flow regulation by uORFs.
- The findings elucidate the mechanism by which uORFs can enhance downstream translation.
- This work provides a simplified yet insightful model for studying translation dynamics.
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