Effects of post-transcriptional regulation on phenotypic noise in Escherichia coli
Effects of post-transcriptional regulation on phenotypic noise in Escherichia coli
复制标题
DOI：
10.1093/nar/gkt184
复制
发表时间：
2013-05-01
影响因子：
14.9
通讯作者：
Stavans, Joel
中科院分区：
文献类型：
--
作者：
Arbel-Goren, Rinat;Tal, Asaf;Stavans, Joel
蛋白质丰度的细胞间差异，称为噪音，引起同基因细胞之间的表型变异。噪声的研究主要集中在转录时引入的随机性，但转录后调控过程对噪声的影响仍然未知。我们研究RyhB，一种小RNA的大肠杆菌产生的铁应力，其下调的靶蛋白的两个表型变异的影响，使用双染色体融合荧光报告和测量活的单个细胞。尽管细胞处于应激中，但每种靶蛋白的总噪声在宽范围的RyhB产生速率上是显著恒定的。事实上，RyhB对两种靶蛋白的协同下调降低了它们水平之间的相关性。因此，压力下表型变异性的增加是通过解耦同一细胞中不同靶蛋白的表达来实现的，而不是通过增加每种蛋白的总噪音来实现的。外在噪声在RyhB产生速率的总范围内对总蛋白噪声提供了主要贡献。随机模拟再现定性的关键特征，我们的观察和显示，前馈循环形成的转录外源性噪声，sRNA及其靶基因表现出强大的噪声过滤能力。
Cell-to-cell variations in protein abundance, called noise, give rise to phenotypic variability between isogenic cells. Studies of noise have focused on stochasticity introduced at transcription, yet the effects of post-transcriptional regulatory processes on noise remain unknown. We study the effects of RyhB, a small-RNA of Escherichia coli produced on iron stress, on the phenotypic variability of two of its downregulated target proteins, using dual chromosomal fusions to fluorescent reporters and measurements in live individual cells. The total noise of each of the target proteins is remarkably constant over a wide range of RyhB production rates despite cells being in stress. In fact, coordinate downregulation of the two target proteins by RyhB reduces the correlation between their levels. Hence, an increase in phenotypic variability under stress is achieved by decoupling the expression of different target proteins in the same cell, rather than by an increase in the total noise of each. Extrinsic noise provides the dominant contribution to the total protein noise over the total range of RyhB production rates. Stochastic simulations reproduce qualitatively key features of our observations and show that a feed-forward loop formed by transcriptional extrinsic noise, an sRNA and its target genes exhibits strong noise filtration capabilities.