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

Xuefeng Zhu,Lihua Chen,Junsheng Yang,Beidong Liu,Qian Liu,Claes M. Gustafsson,Jonas O. P. Carlsten

doi:10.1093/nar/gkv629

Xuefeng Zhu, Lihua Chen + Show 5 more

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https://doi.org/10.1093/nar/gkv629

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Journal: Nucleic acids research	Publication Date: Jul 2, 2015
Citations: 19	License type: CC BY 4.0

Affiliation: University of Gothenburg

Abstract

The Med2, Med3 and Med15 proteins form a heterotrimeric subdomain in the budding yeast Mediator complex. This Med15 module is an important target for many gene specific transcription activators. A previous proteome wide screen in yeast identified Med3 as a protein with priogenic potential. In the present work, we have extended this observation and demonstrate that both Med3 and Med15 form amyloid-like protein aggregates under H2O2 stress conditions. Amyloid formation can also be stimulated by overexpression of Med3 or of a glutamine-rich domain present in Med15, which in turn leads to loss of the entire Med15 module from Mediator and a change in stress response. In combination with genome wide transcription analysis, our data demonstrate that amyloid formation can change the subunit composition of Mediator and thereby influence transcriptional output in budding yeast.

Highlights

Amyloid-like aggregation of soluble proteins can result in cellular toxicity and cause neurodegenerative disorders [1]
In wild-type cells, Mediator is exclusively located to the nucleus, where it overlaps with chromatin [24] and we wondered if cellular stress could change the subcellullar localization of Mediator subunits
We analyzed the chromatin association of Skn7, a transcription activator, which is recruited to Tup1 associated promoters where Mediator is found [26,27]

Summary

Introduction

Amyloid-like aggregation of soluble proteins can result in cellular toxicity and cause neurodegenerative disorders [1]. Amyloid formation may affect proteins involved in different biological functions, such as regulation of transcription and translation fidelity, as well as modulation of stress and drug resistance [2,3,4,5,6]. The infectious form of prions can induce amyloid formation and transform the normal protein into the misfolded, infectious version. Yeast proteins with priogenic potential often contain domains rich in glutamine (Q) and/or asparagine (N). Overexpression of such domains or the entire prion protein can stimulate amyloid formation in vivo [7]

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