GSE210558
Nab6 and Mrn1 regulate the expression of cell wall mRNAs in budding yeast
The fungal cell wall provides protection and structure to cells, and serves as an important target for antifungal compounds. The cell wall integrity (CWI) signaling pathway regulates the transcriptional response to various cell wall stresses, but emerging evidence suggests posttranscriptional pathways play an important complementary role. Here, we show that the RNA-binding proteins (RBPs) Mrn1 and Nab6 specifically target the 3' UTRs of a largely overlapping set of cell wall-associated mRNAs. These mRNAs are downregulated in the absence of Nab6, indicating that Nab6 directly or indirectly stabilizes its target mRNAs. We further show that Nab6 acts in parallel to conventional CWI signaling to maintain adequate expression of cell wall mRNAs. Cells lacking both pathways are hypersensitive to antifungal compounds targeting the cell wall, while deletion of MRN1 partially alleviates the growth and molecular phenotypes associated with the Dnab6 strain. Taken together, our results uncover a novel posttranscriptional pathway which mediates resistance to cell wall stress and antifungal compounds. Overall design: There are 4 CRAC datasets and 50 RNAseq datasets. The CRAC datasets were generated using affinity tagged versions of Mrn1 and Nab6 under standard ('control') conditions in otherwise wild type cells. The RNAseq experiments were prepared from wild type, Dmrn1, Dnab6, Dslt2, and Dnab6Dslt2 cells before and after treatment with 2 µg/mL Congo Red (0, 1, 2, and 4hr). In addition, wild type, Dmrn1, Dnab6, and Dmrn1Dnab6 cells were treated with 60µg/mL Congo Red (0 and 2 hr).