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Open AccessArticle

The Polymorphic PolyQ Tail Protein of the Mediator Complex, Med15, Regulates the Variable Response to Diverse Stresses

Department of Biology, West Virginia University, 53 Campus Drive, Morgantown, WV 26506, USA
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Int. J. Mol. Sci. 2020, 21(5), 1894; https://doi.org/10.3390/ijms21051894
Received: 2 February 2020 / Revised: 4 March 2020 / Accepted: 6 March 2020 / Published: 10 March 2020
(This article belongs to the Special Issue Small Molecules, Influence of Molecular Pathways)
The Mediator is composed of multiple subunits conserved from yeast to humans and plays a central role in transcription. The tail components are not required for basal transcription but are required for responses to different stresses. While some stresses are familiar, such as heat, desiccation, and starvation, others are exotic, yet yeast can elicit a successful stress response. 4-Methylcyclohexane methanol (MCHM) is a hydrotrope that induces growth arrest in yeast. We found that a naturally occurring variation in the Med15 allele, a component of the Mediator tail, altered the stress response to many chemicals in addition to MCHM. Med15 contains two polyglutamine repeats (polyQ) of variable lengths that change the gene expression of diverse pathways. The Med15 protein existed in multiple isoforms and its stability was dependent on Ydj1, a protein chaperone. The protein level of Med15 with longer polyQ tracts was lower and turned over faster than the allele with shorter polyQ repeats. MCHM sensitivity via variation of Med15 was regulated by Snf1 in a Myc-tag-dependent manner. Tagging Med15 with Myc altered its function in response to stress. Genetic variation in transcriptional regulators magnified genetic differences in response to environmental changes. These polymorphic control genes were master variators. View Full-Text
Keywords: Mediator; stress; MCHM; Med15; Snf1; polyQ; protein chaperone; master variator; intrinsically disordered regions; yeast; hydrotrope; transcription factors; Myc tag; inorganic phosphate Mediator; stress; MCHM; Med15; Snf1; polyQ; protein chaperone; master variator; intrinsically disordered regions; yeast; hydrotrope; transcription factors; Myc tag; inorganic phosphate
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MDPI and ACS Style

Gallagher, J.E.G.; Ser, S.L.; Ayers, M.C.; Nassif, C.; Pupo, A. The Polymorphic PolyQ Tail Protein of the Mediator Complex, Med15, Regulates the Variable Response to Diverse Stresses. Int. J. Mol. Sci. 2020, 21, 1894. https://doi.org/10.3390/ijms21051894

AMA Style

Gallagher JEG, Ser SL, Ayers MC, Nassif C, Pupo A. The Polymorphic PolyQ Tail Protein of the Mediator Complex, Med15, Regulates the Variable Response to Diverse Stresses. International Journal of Molecular Sciences. 2020; 21(5):1894. https://doi.org/10.3390/ijms21051894

Chicago/Turabian Style

Gallagher, Jennifer E.G.; Ser, Suk L.; Ayers, Michael C.; Nassif, Casey; Pupo, Amaury. 2020. "The Polymorphic PolyQ Tail Protein of the Mediator Complex, Med15, Regulates the Variable Response to Diverse Stresses" Int. J. Mol. Sci. 21, no. 5: 1894. https://doi.org/10.3390/ijms21051894

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