Transcriptomic study of zinc-deficient Saccharomyces cerevisiae wild-type, atg1Δ, and atg41Δ strains

Purpose: ATG41 is involved both in autophagy and zinc-deficient growth. The goal of this study is to compare transcriptomic profiles of wild-type and atg41Δ strains to discover autophagy-independent molecular phenotypes for the mutant. The atg1Δ mutant is a control for autophagy activity. Methods: Wild-type and mutant yeast were grown to mid-log phase in replete medium and shifted to zinc-deficient medium for 8 hours, after which, cells were harvested for RNA sequencing to detect differential gene expression. Results: Gene expression data for virtually every gene (~6,000) was obtained with ~12,000,000 reads per sample. Differential gene expression analysis showed that several hundred genes were differentially experessed in the atg41Δ mutant (greater than 2-fold) at an FDR of 0.5. Conclusions: Most strikingly, we found that the atg41Δ mutant transcriptome shows signs that sulfur metabolism is distrupted during zinc-deficinet growth. Expression of Met4 gene targets is increased.研究目的：ATG41 同时参与自噬（autophagy）与缺锌生长过程。本研究旨在对比野生型与atg41Δ缺失菌株的转录组谱，以挖掘该突变体中不依赖自噬的分子表型；atg1Δ缺失突变体作为自噬活性的对照菌株。 实验方法：将野生型及突变体酵母在营养充足培养基中培养至对数生长中期，随后转接至缺锌培养基中培养8小时；收集细胞并进行RNA测序（RNA sequencing）以检测差异基因表达情况。 实验结果：本研究获取了几乎全部约6000个基因的表达数据，每个样本的测序读段数约为1200万。差异基因表达分析显示，在错误发现率（FDR, False Discovery Rate）为0.5的条件下，atg41Δ缺失突变体中有数百个基因出现了2倍以上的差异表达。 研究结论：最引人注目的是，我们发现atg41Δ缺失突变体的转录组在缺锌生长过程中存在硫代谢紊乱现象，Met4基因的靶标表达水平显著上调。