title: Different Regulations ofROM2andLRG1Expression by Ccr4, Pop2, and Dhh1 in theSaccharomyces cerevisiaeCell Wall Integrity Pathway.
abstract: Ccr4, a component of the Ccr4-Not cytoplasmic deadenylase complex, is known to be required for the cell wall integrity (CWI) pathway in the budding yeastSaccharomyces cerevisiae. However, it is not fully understood how Ccr4 and other components of the Ccr4-Not complex regulate the CWI pathway. Previously, we showed that Ccr4 functions in the CWI pathway together with Khd1 RNA binding protein. Ccr4 and Khd1 modulate a signal from Rho1 small GTPase in the CWI pathway by regulating the expression ofROM2mRNA andLRG1mRNA, encoding a guanine nucleotide exchange factor (GEF) and a GTPase-activating protein (GAP) for Rho1, respectively. Here we examined the possible involvement of thePOP2gene encoding a subunit of the Ccr4-Not complex and theDHH1gene encoding a DEAD box RNA helicase that associates with the Ccr4-Not complex in the regulation ofROM2andLRG1expression. NeitherROM2mRNA level nor Rom2 function was impaired bypop2Δordhh1Δmutation. TheLRG1mRNA level was increased inpop2Δanddhh1Δmutants, as well as theccr4Δmutant, and the growth defects caused bypop2Δanddhh1Δmutations were suppressed bylrg1Δmutation. Our results suggest thatLRG1expression is regulated by Ccr4 together with Pop2 and Dhh1 and thatROM2expression is regulated by Khd1 and Ccr4, but not by Pop2 and Dhh1. Thus, Rho1 activity in the CWI pathway is precisely controlled by modulation of the mRNA levels for Rho1-GEF Rom2 and Rho1-GAP Lrg1.IMPORTANCEWe find here that Ccr4, Pop2, and Dhh1 modulate the levels of mRNAs for specific Rho1 regulators, Rom2 and Lrg1. In budding yeast, Rho1 activity is tightly regulated both temporally and spatially. It is anticipated that Ccr4, Pop2, and Dhh1 may contribute to the precise spatiotemporal control of Rho1 activity by regulating expression of its regulators temporally and spatially. Our finding on the roles of the components of the Ccr4-Not complex in yeast would give important information for understanding the roles of the evolutionary conserved Ccr4-Not complex.
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ohmori
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Irie
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suda
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Mizuno
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Irie
keywords: Ccr4-Not complex; Rho1; cell wall; mRNA stability; yeasts