Balagopal Vidya, Parker Roy
Department of Molecular and Cellular Biology and Howard Hughes Medical Institute, University of Arizona, Tucson, Arizona 85721-0206, USA.
Genetics. 2009 Jan;181(1):93-103. doi: 10.1534/genetics.108.092601. Epub 2008 Nov 17.
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 5'-3' 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 pat1Delta 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, stm1Delta 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.
mRNA降解和翻译的控制对于基因表达的调控至关重要。mRNA降解通常由去腺苷酸化引发，这会导致脱帽和5'-3'衰变。在芽殖酵母酿酒酵母中，Dhh1和Pat1蛋白促进脱帽，这两种蛋白似乎既抑制翻译起始又促进脱帽。为了了解这些因子的功能，我们鉴定出核糖体结合蛋白Stm1是pat1Delta菌株温度敏感性的多拷贝抑制因子。Stm1功能缺失等位基因和过表达菌株与Pat1和Dhh1等位基因表现出多种遗传相互作用，其方式与Stm1在Dhh1上游起作用以促进Dhh1功能一致。与Stm1影响Dhh1功能一致，stm1Delta菌株在EDC1和COX17 mRNA的降解方面存在缺陷，其衰变受到Dhh1缺失的强烈影响。这些结果确定Stm1是mRNA降解机制的一个额外组成部分，并表明mRNA脱帽与核糖体功能之间可能存在联系。
