Yofe Ido, Zafrir Zohar, Blau Rachel, Schuldiner Maya, Tuller Tamir, Shapiro Ehud, Ben-Yehezkel Tuval
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Department of Biomedical Engineering, Tel-Aviv University, Tel Aviv, Israel.
PLoS Genet. 2014 Jun 26;10(6):e1004407. doi: 10.1371/journal.pgen.1004407. eCollection 2014 Jun.
Introns are key regulators of eukaryotic gene expression and present a potentially powerful tool for the design of synthetic eukaryotic gene expression systems. However, intronic control over gene expression is governed by a multitude of complex, incompletely understood, regulatory mechanisms. Despite this lack of detailed mechanistic understanding, here we show how a relatively simple model enables accurate and predictable tuning of synthetic gene expression system in yeast using several predictive intron features such as transcript folding and sequence motifs. Using only natural Saccharomyces cerevisiae introns as regulators, we demonstrate fine and accurate control over gene expression spanning a 100 fold expression range. These results broaden the engineering toolbox of synthetic gene expression systems and provide a framework in which precise and robust tuning of gene expression is accomplished.
内含子是真核基因表达的关键调控因子，是设计合成真核基因表达系统的一种潜在强大工具。然而，内含子对基因表达的控制受众多复杂且尚未完全理解的调控机制支配。尽管缺乏对其详细机制的了解，但在此我们展示了一个相对简单的模型如何利用转录本折叠和序列基序等几个预测性内含子特征，在酵母中实现对合成基因表达系统的准确且可预测的调控。仅使用天然酿酒酵母内含子作为调控因子，我们证明了能在跨越100倍表达范围的情况下对基因表达进行精细且准确的控制。这些结果拓宽了合成基因表达系统的工程工具箱，并提供了一个实现基因表达精确且稳健调控的框架。
