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Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
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Eukaryotic Polyribosome Profile Analysis
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Controllability Analysis and Control Synthesis for the Ribosome Flow Model.

Yoram Zarai, Michael Margaliot, Eduardo D Sontag

    IEEE/ACM Transactions on Computational Biology and Bioinformatics
    |May 26, 2017
    PubMed
    Summary

    Regulating mRNA translation using the ribosome flow model (RFM) allows precise control over protein production rates and ribosomal density. This study demonstrates controllability, enabling targeted adjustments for desired biological outcomes.

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    Area of Science:

    • Systems Biology
    • Computational Biology
    • Biophysics

    Background:

    • Ribosomal density along mRNA influences protein production, folding, and degradation.
    • Controlling translation is crucial for cellular function and organismal fitness.
    • The ribosome flow model (RFM) is a dynamical system for studying mRNA translation.

    Purpose of the Study:

    • To investigate the control of ribosomal density profiles along mRNA using the RFM.
    • To determine time-varying transition rates that steer the system to a desired ribosomal density.
    • To analyze two distinct control problems with varying regulation capabilities.

    Main Methods:

    • Modeling mRNA translation as a chain of sites with state variables for ribosomal density.
    • Utilizing transition rates between sites as control parameters.
    • Analyzing system controllability and deriving control functions for specific scenarios.

    Main Results:

    • Demonstrated that the RFM system is controllable, allowing steering to desired ribosomal density profiles.
    • Provided closed-form expressions for constant control functions to achieve desired states.
    • Developed an algorithm for determining control values in a second, more constrained control problem.

    Conclusions:

    • The RFM provides a framework for understanding and controlling mRNA translation dynamics.
    • Precise regulation of ribosomal density is achievable, with implications for protein synthesis and cellular processes.
    • The study offers insights into the biological significance of translation control mechanisms.