Stm1 Modulates mRNA Decay and Dhh1 Function in Saccharomyces cerevisiae

Abstract

The control of mRNA degradation and translation are important for the regulation of gene expression. mRNA degradation is often initiated by deadenylation, which leads to decapping and 59-39 decay. In the budding yeast Saccharomyces cerevisae, decapping is promoted by the Dhh1 and Pat1 proteins, which appear to both inhibit translation initiation and promote decapping. To understand the function of these factors, we identified the ribosome binding protein Stm1 as a multicopy suppressor of the temperature sensitivity of the pat1D strain. Stm1 loss-of-function alleles and overexpression strains show several genetic interactions with Pat1 and Dhh1 alleles in a manner consistent with Stm1 working upstream of Dhh1 to promote Dhh1 function. Consistent with Stm1 affecting Dhh1 function, stm1D strains are defective in the degradation of the EDC1 and COX17 mRNAs, whose decay is strongly affected by the loss of Dhh1. These results identify Stm1 as an additional component of the mRNA degradation machinery and suggest a possible connection of mRNA decapping to ribosome function.

Distinct functions of maternal and somatic Pat1 protein paralogs

“…However, unlike FMRP, a well-characterized RNA-binding protein, which interacts with G-quartet RNA via an RGG box (Darnell et al 2001;Schaeffer et al 2001;Zanotti et al 2006), no such sequences are present in Pat1 proteins. Interestingly, the yeast protein Stm1 also interacts with G-quadruplex, promotes the accumulation of Dhh1 (Xp54 homolog) in P-bodies, and modulates Dhh1 function (Van Dyke et al 2004;Balagopal and Parker 2009). …”

Telomerase Is Essential to Alleviate Pif1-Induced Replication Stress at Telomeres

“…Lack of Stm1 may weaken telomere capping and cause sensitivity to PIF1 overexpression. However, Stm1 also has functions in mRNA decay and protein synthesis (Van Dyke et al 2006;Balagopal and Parker 2009) so it may protect cells from damage induced by PIF1 overexpression through other mechanisms not related to telomere maintenance.…”

Structural and functional analysis of Nro1/Ett1: a protein involved in translation termination in S. cerevisiae and in O2-mediated gene control in S. pombe

“…The YOR051C encoded protein also inhibits the replication of Brome mosaic virus in S. cerevisiae similarly to genes coding for proteins involved in mRNA metabolism (Ski complex and Ski7) (Kushner et al 2003). Finally, this protein copurifies with ribosomal proteins together with Stm1 (Van Dyke et al 2004), a protein modulating mRNA decay (Balagopal and Parker 2009) and involved in TOR signaling. Based on the established links between YOR051C and Tpa1 and between their homologs Ofd1 and Nro1 in S. pombe, as well as on the effect of Tpa1 on translation termination efficiency, we have previously tested the effect of YOR051C deletion on stop codon read-through in S. cerevisiae and observed a similar, albeit weaker, phenotype as TPA1 gene deletion (i.e., a significant increase of stop-codon read-through).…”