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Updated: Oct 12, 2025
Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
Published on: January 8, 2015
Vectorial channeling as a mechanism for translational control by functional prions and condensates
Xinyu Gu1,2, Nicholas P Schafer1,2, Peter G Wolynes3,2
1Center for Theoretical Biological Physics, Rice University, Houston, TX 77005.
Abstract:
Translation of messenger RNA (mRNA) is regulated through a diverse set of RNA-binding proteins. A significant fraction of RNA-binding proteins contains prion-like domains which form functional prions. This raises the question of how prions can play a role in translational control. Local control of translation in dendritic spines by prions has been invoked in the mechanism of synaptic plasticity and memory. We show how channeling through diffusion and processive translation cooperate in highly ordered mRNA/prion aggregates as well as in less ordered mRNA/protein condensates depending on their substructure. We show that the direction of translational control, whether it is repressive or activating, depends on the polarity of the mRNA distribution in mRNA/prion assemblies which determines whether vectorial channeling can enhance recycling of ribosomes. Our model also addresses the effect of changes of substrate concentration in assemblies that have been suggested previously to explain translational control by assemblies through the introduction of a potential of mean force biasing diffusion of ribosomes inside the assemblies. The results from the model are compared with the experimental data on translational control by two functional RNA-binding prions, CPEB involved in memory and Rim4 involved in gametogenesis.
Insights
Functional prions regulate messenger RNA (mRNA) translation. Their structure dictates whether translation is repressed or activated, impacting synaptic plasticity and memory formation.
Area of Science:
- Molecular Biology
- Neuroscience
- Biophysics
Background:
- RNA-binding proteins, many with prion-like domains, regulate messenger RNA (mRNA) translation.
- Functional prions are implicated in cellular processes, including translational control.
- Prions in dendritic spines are hypothesized to mediate synaptic plasticity and memory.
Purpose of the Study:
- To investigate the mechanism by which prions regulate mRNA translation.
- To model how the structure of mRNA/prion assemblies influences translational control.
- To determine the role of mRNA distribution polarity and ribosome dynamics in translational regulation.
Main Methods:
- Development of a theoretical model for mRNA/prion condensate substructure.
- Analysis of diffusion, processive translation, and ribosome recycling within assemblies.
- Incorporation of a potential of mean force to model ribosome diffusion bias.
- Comparison of model predictions with experimental data for CPEB and Rim4 prions.
Main Results:
- Translational control direction (repressive/activating) depends on mRNA distribution polarity within assemblies.
- Vectorial channeling of ribosomes is enhanced by specific mRNA polarities, influencing ribosome recycling.
- Substrate concentration changes within assemblies affect ribosome diffusion and translational output.
- The model successfully explains experimental observations for CPEB and Rim4 functional prions.
Conclusions:
- Prion-based translational control is mechanistically linked to the ordered structure of mRNA/prion assemblies.
- The polarity of mRNA distribution within these assemblies is a key determinant of translational regulation.
- This work provides a framework for understanding prion function in gene expression and cellular processes like memory and gametogenesis.
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