S. cerevisiae Mub1, a substrate adaptor of E3 ubiquitin ligase, modulates sensitivity to cell wall stressors through multiple transcription factors

Yeasts evolved a complex regulatory program to build and maintain their cell wall, the primary structure through which they interact with their environment. However, how this program ties to essential cellular processes mostly remains unclear. Here, we focus on Saccharomyces cerevisiae Mub1, an adaptor protein of E3 ubiquitin ligase Ubr2, previously associated with regulating proteasome genes through transcription factor Rpn4. We show that S. cerevisiae cells lacking Mub1 become hyper-tolerant to standard cell wall stressors, outperforming wild-type cells. This protective mub1Δ phenotype stems from the activity of several transcription factors, leading to the inhibition of cell wall remodelling, a typically protective process that becomes maladaptive during chronic cell wall stress in laboratory conditions. Based on these results, we suggest Mub1 regulates not only Rpn4 but a much broader range of transcription factors and thus serves as an in-so-far unrecognised regulatory hub directly linking cell wall robustness with the ubiquitin-proteasome system. To investigate the source of the mub1Δ phenotype, we grew exponential phase S. cerevisiae wild type (BMA41) and its mub1Δ derivative for 5 hours, either in standard chemically defined yeast medium or standard chemically defined yeast medium supplemented with 20 µg/ml Calcofluor white. We then performed gene expression profilling analysis using RNA-seq data for all four conditions, in duplicates. RNA-seq reads were mapped with HISAT2 2.2.1, using default parameters, and count matrices produced with featureCounts 2.0.3.