Actin remodelling controls proteasome homeostasis upon stress

Area of Science:

• Cellular Biology
• Molecular Biology
• Stress Response Mechanisms

Background:

• Cellular stress often leads to reduced bulk translation and increased synthesis of stress-response proteins.
• 19S regulatory-particle assembly chaperones (RPACs) are selectively translated upon TORC1 inhibition to maintain proteasome function and cell viability.
• The precise molecular mechanisms governing this selective translational upregulation remain largely unknown.

Purpose of the Study:

• To elucidate the molecular mechanism behind the selective translational upregulation of RPACs under cellular stress.
• To investigate the role of the actin cytoskeleton in stress-induced translational control.
• To identify key proteins involved in the localization and translation of stress-response mRNAs.

Main Methods:

• Utilized yeast as a model organism to study stress response pathways.
• Investigated the association of RPAC mRNA (ADC17) with cytoskeletal structures under stress conditions.
• Examined the role of the early endocytic protein Ede1 in RPAC mRNA localization and translation.
• Experimentally tethered ADC17 mRNA to cortical actin patches to assess translational effects.

Main Results:

• Discovered that actin cytoskeleton remodeling is essential for RPAC translation following TORC1 inhibition.
• Found ADC17 mRNA associated with actin cables and enriched at cortical actin patches under stress, dependent on Ede1.
• Observed that ede1∆ cells failed to induce RPACs and proteasome assembly upon TORC1 inhibition.
• Demonstrated that artificial tethering of ADC17 mRNA to cortical actin patches enhanced its translation under stress.

Conclusions:

• Actin-dense structures, such as cortical actin patches, can act as translation platforms for specific stress-induced mRNAs.
• The early endocytic protein Ede1 is critical for the stress-induced relocation and translation of RPAC mRNAs.
• This mechanism highlights a novel role for the actin cytoskeleton in regulating proteasome homeostasis during cellular stress.