Identification of <i>ebs1</i>, <i>lsm6</i> and <i>nup159</i> as suppressors of <i>spt</i>10 effects at <i>ADH</i>2 in <i>Saccharomyces cerevisiae</i> suggests post-transcriptional defects affect mRNA synthesis

Abstract

Suppression of the effects of an spt 10 mutation on ADH 2 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 ( CCR 4, CAF 1, NOT 4) or have been shown to interact with the complex ( DBF 2, SRB 9, SRB 10). In this work, we conducted a screen for additional suppressors of spt 10 at ADH 2 to identify new factors related to CCR4 function. In addition to reisolating ccr 4 and caf 1 alleles, three previously unidentified suppressors of spt 10 were obtained: ebs 1, lsm 6, and nup 159. These three genes are known or presumed to affect mRNA export or degradation. Mutations in EBS 1, LSM 6 and NUP 159 not only suppressed spt 10-induced ADH 2 expression but also, like ccr 4 and caf1 defects, reduced the ability of ADH 2 to derepress. None of these defects affected the expression of CCR4-NOT complex components or the formation of the CCR4-NOT complex. The reduced ADH 2 expression was also not the result of increased degradation of ADH 2 mRNA, as the lsm 6 and nup 159 alleles, like that of a ccr 4 deletion, actually slowed ADH 2 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.