Yeast Terminator Function Can Be Modulated and Designed on the Basis of Predictions of Nucleosome Occupancy,ACS Synthetic Biology

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Yeast Terminator Function Can Be Modulated and Designed on the Basis of Predictions of Nucleosome Occupancy
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2017-08-17 00:00:00 , DOI: 10.1021/acssynbio.7b00138
Nicholas J. Morse ₁ , Madan R. Gopal ₁ , James M. Wagner ₁ , Hal S. Alper _{1,

2}

Affiliation

The design of improved synthetic parts is a major goal of synthetic biology. Mechanistically, nucleosome occupancy in the 3′ terminator region of a gene has been found to correlate with transcriptional expression. Here, we seek to establish a predictive relationship between terminator function and predicted nucleosome positioning to design synthetic terminators in the yeast Saccharomyces cerevisiae. In doing so, terminators improved net protein output from these expression cassettes nearly 4-fold over their original sequence with observed increases in termination efficiency to 96%. The resulting terminators were indeed depleted of nucleosomes on the basis of mapping experiments. This approach was successfully applied to synthetic, de novo, and native terminators. The mode of action of these modifications was mainly through increased termination efficiency, rather than half-life increases, perhaps suggesting a role in improved mRNA maturation. Collectively, these results suggest that predicted nucleosome depletion can be used as a heuristic approach for improving terminator function, though the underlying mechanism remains to be shown.

中文翻译：

可以根据核小体的占有率预测来设计酵母终止子的功能

改进的合成部件的设计是合成生物学的主要目标。从机理上讲，已经发现基因3'终止子区域中核小体的占有与转录表达相关。在这里，我们寻求建立终止子功能和预测的核小体定位之间的预测关系，以设计酿酒酵母中的合成终止子。这样，终止子使从这些表达盒输出的净蛋白质量比其原始序列提高了近4倍，并且观察到的终止效率提高到96％。在作图实验的基础上，所得的终止子确实耗尽了核小体。此方法已成功应用于合成，从头开始以及本地终止符。这些修饰的作用方式主要是通过提高终止效率，而不是通过增加半衰期来实现的，这可能暗示了其在改善mRNA成熟度方面的作用。总体而言，这些结果表明，预测的核小体耗竭可以用作改善终止子功能的启发式方法，尽管其潜在机理尚待证实。

更新日期：2017-08-17

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