Bird Amanda J, Labbé Simon
Departments of Human Nutrition and Molecular Genetics, The Ohio State University, 1787 Neil Avenue, Columbus, OH 43210, USA.
Département de Biochimie, Faculté de médecine et des sciences de la santé, Pavillon Z-8, 3201, Jean Mignault, Sherbrooke, QC J1E 4K8, Canada.
Mol Microbiol. 2017 Dec;106(5):673-677. doi: 10.1111/mmi.13856. Epub 2017 Oct 26.
The zinc-responsive transcription activator Zap1 plays a central role in zinc homeostasis in the budding yeast Saccharomyces cerevisiae. In zinc-deficient cells, Zap1 binds to zinc responsive elements in target gene promoters and activates gene expression. In most cases, Zap1-dependent gene activation results in increased levels of mRNAs and proteins. However, Zap1-dependent activation of RTC4 results in increased levels of the RTC4 mRNA and decreased levels of the Rtc4 protein. This atypical regulation results from Zap1-mediated changes in the transcriptional start site for RTC4 and the production of a RTC4 transcript with a longer 5' leader. This long RTC4 transcript contains small upstream open reading frames that prevent translation of the downstream RTC4 ORF. The new studies with Zap1 highlight how a transcriptional activator can facilitate decreased protein expression.
锌响应转录激活因子Zap1在出芽酵母酿酒酵母的锌稳态中起着核心作用。在缺锌细胞中，Zap1与靶基因启动子中的锌响应元件结合并激活基因表达。在大多数情况下，Zap1依赖的基因激活导致mRNA和蛋白质水平增加。然而，Zap1依赖的RTC4激活导致RTC4 mRNA水平增加和Rtc4蛋白水平降低。这种非典型调节是由Zap1介导的RTC4转录起始位点的变化以及产生具有更长5'前导序列的RTC4转录本引起的。这个长的RTC4转录本包含小的上游开放阅读框，阻止下游RTC4开放阅读框的翻译。关于Zap1的新研究突出了转录激活因子如何促进蛋白质表达的降低。
