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Updated: Jan 7, 2026
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Measuring Transcellular Interactions through Protein Aggregation in a Heterologous Cell System
Published on: May 22, 2020
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Human RBM3 protein is prone to form neuronal aggregates opposed by the proteasome
Suman Kumar1, Tina Kleven1, Rafal Ciosk1
1Section for Biochemistry and Molecular Biology, Department of Biosciences, University of Oslo, Oslo 0316, Norway.
Biology Open
|December 12, 2025
Summary
Human neurons show cold-induced aggregation of RNA-binding motif protein 3 (RBM3), a key factor in neuroprotection. This aggregation, counteracted by the proteasome, offers insights into neuronal proteostasis and hypothermia treatments.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Proteostasis is vital for neuronal function; its disruption causes neurodegeneration.
- Cold exposure offers neuroprotection, partly via cold-inducible RNA-binding motif protein 3 (RBM3) in rodents.
- The impact of hypothermia on neuronal proteostasis and RBM3 function in humans is not well understood.
Purpose of the Study:
- To investigate the behavior of human RBM3 in neurons under hypothermia.
- To determine the relationship between RBM3 aggregation, proteasomal activity, and neuronal health.
- To explore evolutionary adaptations in RBM3 related to temperature fluctuations.
Main Methods:
- Cultured human neurons subjected to profound hypothermia.
- Analysis of RBM3 aggregation patterns.
- Investigation of RBM3 aggregation under proteasomal inhibition at physiological temperatures.
- Comparative analysis of RBM3 proteins from hibernating and non-hibernating mammals.
Main Results:
- Profound hypothermia induced aggregation of human RBM3 in cultured neurons.
- RBM3 aggregates were distinct from stress granules and specific to differentiated neurons.
- RBM3 aggregation also occurred at physiological temperatures when proteasomal activity was inhibited.
- Variations in RBM3 suggest mechanisms to prevent aggregation in animals with fluctuating body temperatures.
Conclusions:
- Human RBM3 undergoes cold-induced aggregation in neurons, a process potentially managed by the proteasome.
- Understanding RBM3 aggregation is crucial for neuronal proteostasis and has implications for hypothermia-related medical treatments.
- Evolutionary differences in RBM3 may explain its resilience in animals experiencing temperature changes.
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