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Updated: Jul 10, 2025
Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling
Published on: October 28, 2014
The ribosome-associated chaperone Zuo1 controls translation upon TORC1 inhibition
Ailsa Black1, Thomas D Williams1, Flavie Soubigou1
1MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, UK.
Abstract:
Protein requirements of eukaryotic cells are ensured by proteostasis, which is mediated by tight control of TORC1 activity. Upon TORC1 inhibition, protein degradation is increased and protein synthesis is reduced through inhibition of translation initiation to maintain cell viability. Here, we show that the ribosome-associated complex (RAC)/Ssb chaperone system, composed of the HSP70 chaperone Ssb and its HSP40 co-chaperone Zuo1, is required to maintain proteostasis and cell viability under TORC1 inhibition in Saccharomyces cerevisiae. In the absence of Zuo1, translation does not decrease in response to the loss of TORC1 activity. A functional interaction between Zuo1 and Ssb is required for proper translational control and proteostasis maintenance upon TORC1 inhibition. Furthermore, we have shown that the rapid degradation of eIF4G following TORC1 inhibition is mediated by autophagy and is prevented in zuo1Δ cells, contributing to decreased survival in these conditions. We found that autophagy is defective in zuo1Δ cells, which impedes eIF4G degradation upon TORC1 inhibition. Our findings identify an essential role for RAC/Ssb in regulating translation in response to changes in TORC1 signalling.
Insights
The ribosome-associated complex (RAC)/Ssb chaperone system, including Zuo1, is crucial for maintaining cell viability under TORC1 inhibition by regulating protein synthesis and degradation. Its absence impairs proteostasis and survival in yeast.
Area of Science:
- Cellular biology
- Molecular biology
- Biochemistry
Background:
- Proteostasis is vital for eukaryotic cell survival, regulated by TORC1 signaling.
- TORC1 inhibition triggers reduced protein synthesis and increased degradation.
- The ribosome-associated complex (RAC)/Ssb chaperone system's role in this process is unclear.
Purpose of the Study:
- To investigate the role of the RAC/Ssb chaperone system in maintaining proteostasis under TORC1 inhibition.
- To elucidate the mechanism by which RAC/Ssb influences translation and cell viability.
Main Methods:
- Studied Saccharomyces cerevisiae (yeast) models with genetic modifications.
- Analyzed protein synthesis, degradation, and cell viability under TORC1 inhibition.
- Investigated the interaction between Zuo1, Ssb, and the autophagy pathway.
Main Results:
- The RAC/Ssb system, particularly Zuo1, is essential for decreasing translation upon TORC1 inhibition.
- Zuo1 is required for proper proteostasis and cell viability under these conditions.
- Autophagy defects in zuo1Δ cells impede eIF4G degradation, impacting survival.
Conclusions:
- The RAC/Ssb chaperone system plays a critical role in regulating translation in response to TORC1 signaling.
- Zuo1 mediates translational control and proteostasis maintenance upon TORC1 inhibition.
- RAC/Ssb influences cell viability through its impact on protein synthesis, degradation, and autophagy.
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