Heat Shock Response in Yeast Involves Changes in Both Transcription Rates and mRNA Stabilities

We have analyzed the heat stress response in the yeast Saccharomyces cerevisiae by determining mRNA levels and transcription rates for the whole transcriptome after a shift from 25°C to 37°C. Using an established mathematical algorithm, theoretical mRNA decay rates have also been calculated from the experimental data. We have verified the mathematical predictions for selected genes by determining their mRNA decay rates at different times during heat stress response using the regulatable tetO promoter. This study indicates that the yeast response to heat shock is not only due to changes in transcription rates, but also to changes in the mRNA stabilities. mRNA stability is affected in 62% of the yeast genes and it is particularly important in shaping the mRNA profile of the genes belonging to the environmental stress response. In most cases, changes in transcription rates and mRNA stabilities are homodirectional for both parameters, although some interesting cases of antagonist behavior are found. The statistical analysis of gene targets and sequence motifs within the clusters of genes with similar behaviors shows that both transcriptional and post-transcriptional regulons apparently contribute to the general heat stress response by means of transcriptional factors and RNA binding proteins.

本研究通过检测酿酒酵母（Saccharomyces cerevisiae）从25℃升温至37℃后全转录组的mRNA水平与转录速率，分析了其热应激响应过程。借助已确立的数学算法，本研究从实验数据中推算得到了理论mRNA降解速率。本研究通过使用可调控tetO启动子，检测热应激响应过程中不同时间点部分基因的mRNA降解速率，从而验证了前述数学预测结果。本研究表明，酿酒酵母的热休克响应不仅由转录速率的变化所介导，同时也与mRNA稳定性的改变息息相关。62%的酿酒酵母基因的mRNA稳定性受到调控，且其在塑造环境应激响应相关基因的mRNA表达谱过程中发挥着尤为关键的作用。在绝大多数情况下，转录速率与mRNA稳定性的变化呈同向趋势，但也存在少量有趣的二者变化方向相悖的案例。对具有相似表达模式的基因簇内的基因靶标与序列基序开展统计分析后发现，转录调控子与转录后调控子均可通过转录因子与RNA结合蛋白的介导，共同参与整体热应激响应过程。