A posttranscriptional pathway regulates cell wall mRNA expression in budding yeast

The fungal cell wall provides protection and structure and is an important target for antifungal compounds. A mitogen-activated protein (MAP) kinase cascade termed the cell wall integrity (CWI) pathway regulates transcriptional responses to cell wall damage. Here, we describe a posttranscriptional pathway that plays an important complementary role. We report that the RNA-binding proteins (RBPs) Mrn1 and Nab6 specifically target the 30 UTRs of a largely overlapping set of cell wall-related mRNAs. These mRNAs are downregulated in the absence of Nab6, indicating a function in target mRNA stabilization. Nab6 acts in parallel to CWI signaling to maintain appropriate expression of cell wall genes during stress. Cells lacking both pathways are hypersensitive to antifungal compounds targeting the cell wall. Deletion of MRN1 partially alleviates growth defects associated with Delta nab6, and Mrn1 has an opposing function in mRNA destabilization. Our results un-cover a posttranscriptional pathway that mediates cellular resistance to antifungal compounds.

Automated summary

The fungal cell wall is a crucial target for antifungal compounds, and the cell wall integrity (CWI) pathway regulates transcriptional responses to cell wall damage. In addition, RNA-binding proteins Mrn1 and Nab6 play a complementary role by stabilizing cell wall-related mRNAs. Lack of Nab6 leads to downregulation of these mRNAs, while CWI signaling and Nab6 work together to maintain appropriate cell wall gene expression during stress. Deletion of MRN1 partially alleviates the growth defects associated with Delta nab6, indicating an opposing function in mRNA destabilization. Our findings highlight the importance of a posttranscriptional pathway in cellular resistance to antifungal compounds.