Identification of ebs1, lsm6 and nup159 as suppressors of spt10 effects at ADH2 in Saccharomyces cerevisiae suggests post-transcriptional defects affect mRNA synthesis

Abstract

Suppression of the effects of an spt10 mutation on ADH2 expression is a phenotype shared by a small number of genes whose protein products are either components of the CCR4-NOT complex required for mRNA deadenylation and degradation (CCR4, CAF1, NOT4) or have been shown to interact with the complex (DBF2, SRB9, SRB10). In this work, we conducted a screen for additional suppressors of spt10 at ADH2 to identify new factors related to CCR4 function. In addition to reisolating ccr4 and caf1 alleles, three previously unidentified suppressors of spt10 were obtained: ebs1, lsm6, and nup159. These three genes are known or presumed to affect mRNA export or degradation. Mutations in EBS1, LSM6 and NUP159 not only suppressed spt10-induced ADH2 expression but also, like ccr4 and caf1 defects, reduced the ability of ADH2 to derepress. None of these defects affected the expression of CCR4-NOT complex components or the formation of the CCR4-NOT complex. The reduced ADH2 expression was also not the result of increased degradation of ADH2 mRNA, as the lsm6 and nup159 alleles, like that of a ccr4 deletion, actually slowed ADH2 degradation. Our results indicate that alterations in factors that slow mRNA degradation or affect mRNA transport may also interfere with the synthesis of mRNA and suggest an integration of such events in gene expression.