欧洲分子生物学实验室Lars M. Steinmetz及其团队的研究发现转录邻域调节转录亚型的长度和表达水平。这一研究成果于2022年3月4日发表在国际学术期刊《科学》上。

研究人员使用具有随机重新定位基因的合成酵母菌株系统地探究了序列和转录环境的影响。研究人员分析了612个基因组扰动中1.2亿个全长转录分子，观察到基因表达水平和转录亚型边界的序列独立变化，这些变化受相邻转录的影响。研究确定了可以预测这些改变的转录背景特征，并使用这些特征来设计一个合成电路，其中转录长度由相邻转录控制。该研究展示了如何在合成基因组工程中利用空间位置优化转录。

据了解，基因序列特征及其侧翼调控区是RNA转录亚型表达的决定因素，并在合成生物学中用作独立的即插即用模块。然而，遗传背景-包括相邻的转录环境-也会影响转录亚型的表达水平和边界。

附：英文原文

Title: Transcriptional neighborhoods regulate transcript isoform lengths and expression levels

Author: Aaron N. Brooks, Amanda L. Hughes, Sandra Clauder-Münster, Leslie A. Mitchell, Jef D. Boeke, Lars M. Steinmetz

Issue&Volume: 2022-03-04

Abstract: Sequence features of genes and their flanking regulatory regions are determinants of RNA transcript isoform expression and have been used as context-independent plug-and-play modules in synthetic biology. However, genetic context—including the adjacent transcriptional environment—also influences transcript isoform expression levels and boundaries. We used synthetic yeast strains with stochastically repositioned genes to systematically disentangle the effects of sequence and context. Profiling 120 million full-length transcript molecules across 612 genomic perturbations, we observed sequence-independent alterations to gene expression levels and transcript isoform boundaries that were influenced by neighboring transcription. We identified features of transcriptional context that could predict these alterations and used these features to engineer a synthetic circuit where transcript length was controlled by neighboring transcription. This demonstrates how positional context can be leveraged in synthetic genome engineering.

DOI: abg0162

Source: https://www.science.org/doi/10.1126/science.abg0162