RNA-Binding Protein Khd1 and Ccr4 Deadenylase Play Overlapping Roles in the Cell Wall Integrity Pathway in Saccharomyces cerevisiae

The Saccharomyces cerevisiae RNA-binding protein Khd1/Hek2 associates with hundreds of potential mRNA targets preferentially, including the mRNAs encoding proteins localized to the cell wall and plasma membrane. We have previously revealed that Khd1 positively regulates expression of MTL1 mRNA encoding a membrane sensor in the cell wall integrity (CWI) pathway. However, a khd1 Delta mutation has no detectable phenotype on cell wall synthesis. Here we show that the khd1 Delta mutation causes a severe cell lysis when combined with the deletion of the CCR4 gene encoding a cytoplasmic deadenylase. We identified the ROM2 mRNA, encoding a guanine nucleotide exchange factor (GEF) for Rho1, as a target for Khd1 and Ccr4. The ROM2 mRNA level was decreased in the khd1 Delta ccr4 Delta mutant, and ROM2 overexpression suppressed the cell lysis of the khd1 Delta ccr4 Delta mutant. We also found that Ccr4 negatively regulates expression of the LRG1 mRNA encoding a GTPase-activating protein (GAP) for Rho1. The LRG1 mRNA level was increased in the ccr4 Delta and khd1 Delta ccr4 Delta mutants, and deletion of LRG1 suppressed the cell lysis of the khd1 Delta ccr4 Delta mutant. Our results presented here suggest that Khd1 and Ccr4 modulate a signal from Rho1 in the CWI pathway by regulating the expression of RhoGEF and RhoGAP.