Mediator tail subunits can form amyloid-like aggregates in vivo and affect stress response in yeast

Xuefeng Zhu1, Lihua Chen2, Jonas O P Carlsten1

  • 1Institute of Biomedicine, University of Gothenburg, P.O. Box 440, SE-405 30 Göteborg, Sweden.

Insights

Budding yeast Med3 and Med15 proteins form amyloid aggregates under stress, impacting Mediator complex composition and altering stress response gene expression.

Area of Science:

  • Molecular Biology
  • Yeast Genetics
  • Protein Aggregation

Background:

  • The Mediator complex is crucial for gene transcription regulation in yeast.
  • Med2, Med3, and Med15 proteins form a key heterotrimeric module within the Mediator complex.
  • Med15 is a known target for transcription activators, and Med3 was previously identified as having aggregation potential.

Purpose of the Study:

  • To investigate the aggregation behavior of Med3 and Med15 proteins under stress conditions.
  • To determine the consequences of Med3 and Med15 aggregation on Mediator complex integrity and function.
  • To explore the impact of altered Mediator composition on yeast stress response.

Main Methods:

  • Induction of protein aggregation using hydrogen peroxide (H2O2) stress.
  • Overexpression of Med3 and a glutamine-rich domain of Med15.
  • Analysis of Mediator complex subunit composition.
  • Genome-wide transcription analysis to assess stress response changes.

Main Results:

  • Med3 and Med15 proteins form amyloid-like aggregates under H2O2 stress.
  • Overexpression of Med3 or Med15's glutamine-rich domain promotes aggregation.
  • Amyloid formation leads to the dissociation of the Med15 module from the Mediator complex.
  • Changes in Mediator subunit composition result in altered stress response gene expression.

Conclusions:

  • Amyloid formation of Med3 and Med15 is a stress-induced phenomenon in budding yeast.
  • Mediator complex subunit composition can be dynamically altered by protein aggregation.
  • This alteration in Mediator structure influences the transcriptional output and stress adaptation of yeast cells.

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