Functional characterization of bacterial sRNAs using a network biology approach
Functional characterization of bacterial sRNAs using a network biology approach
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DOI：
10.1073/pnas.1104318108
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发表时间：
2011-09-13
影响因子：
11.1
通讯作者：
Collins, James J.
中科院分区：
文献类型：
--
作者：
Modi, Sheetal R.;Camacho, Diogo M.;Collins, James J.
小RNA (sRNA) 是转录后调控的重要组成部分。这些分子普遍存在于细菌和真核生物中，并参与对环境应激的多种反应。 sRNA 的功能表征具有挑战性，需要高度集中和广泛的实验程序。在这里，我们利用网络生物学方法和基因表达谱概要，预测了 sRNA 在大肠杆菌中的功能作用和调控相互作用。我们通过实验验证了推断网络中三种 sRNA 的预测：IsrA、GlmZ 和 GcvB。具体来说，我们验证了 IsrA 和 GlmZ 在 SOS 反应中的预测作用，并扩展了 GcvB sRNA 的现有知识，证明了其在调节氨基酸代谢和转运中的广泛作用。我们还使用推断网络与实验相结合表明，GcvB 和 Lrp（一种转录因子）在相互抑制网络中相互抑制。这项工作表明，基于网络的方法可用于识别 sRNA 的细胞功能并表征 sRNA 与转录因子之间的关系。
Small RNAs (sRNAs) are important components of posttranscriptional regulation. These molecules are prevalent in bacterial and eukaryotic organisms, and involved in a variety of responses to environmental stresses. The functional characterization of sRNAs is challenging and requires highly focused and extensive experimental procedures. Here, using a network biology approach and a compendium of gene expression profiles, we predict functional roles and regulatory interactions for sRNAs in Escherichia coli. We experimentally validate predictions for three sRNAs in our inferred network: IsrA, GlmZ, and GcvB. Specifically, we validate a predicted role for IsrA and GlmZ in the SOS response, and we expand on current knowledge of the GcvB sRNA, demonstrating its broad role in the regulation of amino acid metabolism and transport. We also show, using the inferred network coupled with experiments, that GcvB and Lrp, a transcription factor, repress each other in a mutually inhibitory network. This work shows that a network-based approach can be used to identify the cellular function of sRNAs and characterize the relationship between sRNAs and transcription factors.