Working Paper Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 2 February 2020 / Approved: 3 February 2020 / Online: 3 February 2020 (13:37:07 CET)

A peer-reviewed article of this Preprint also exists.

Gallagher, J.E.; 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. Gallagher, J.E.; 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.

Journal reference: Int. J. Mol. Sci. 2020, 21, 1894
DOI: 10.3390/ijms21051894

Abstract

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 response 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. 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. Med15 protein existed in multiple isoforms and its stability was dependent on Ydj1, a protein chaperone. The protein level of the 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 magnifies genetic differences in response to environmental changes. These polymorphic control genes are master variators.

Subject Areas

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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