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Modularity of Escherichia coli sRNA regulation revealed by sRNA-target and protein network analysis

机译:sRNA靶标和蛋白质网络分析揭示了大肠杆菌sRNA调控的模块化

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Background sRNAs, which belong to the non-coding RNA family and range from approximately 50 to 400 nucleotides, serve various important gene regulatory roles. Most are believed to be trans -regulating and function by being complementary to their target mRNAs in order to inhibiting translation by ribosome occlusion. Despite this understanding of their functionality, the global properties associated with regulation by sRNAs are not yet understood. Here we use topological analysis of sRNA targets in terms of protein-protein interaction and transcription-regulatory networks in Escherichia coli to shed light on the global correlation between sRNA regulation and cellular control networks. Results The analysis of sRNA targets in terms of their networks showed that some specific network properties could be identified. In protein-protein interaction network, sRNA targets tend to occupy more central positions (higher closeness centrality, p-val = 0.022) and more cliquish (larger clustering coefficient, p-val = 0.037). The targets of the same sRNA tend to form a network module (shorter characteristic path length, p-val = 0.015; larger density, p-val = 0.019; higher in-degree ratio, p-val = 0.009). Using the transcription-regulatory network, sRNA targets tend to be under multiple regulation (higher indegree, p-val = 0.013) and the targets usually are important to the transfer of regulatory signals (higher betweenness, p-val = 0.012). As was found for the protein-protein interaction network, the targets that are regulated by the same sRNA also tend to be closely knit within the transcription-regulatory network (larger density, p-val = 0.036), and inward interactions between them are greater than the outward interactions (higher in-degree ratio, p-val = 0.023). However, after incorporating information on predicted sRNAs and down-stream targets, the results are not as clear-cut, but the overall network modularity is still evident. Conclusions Our results indicate that sRNA targeting tends to show a clustering pattern that is similar to the human microRNA regulation associated with protein-protein interaction network that was observed in a previous study. Namely, the sRNA targets show close interaction and forms a closely knit network module for both the protein-protein interaction and the transcription-regulatory networks. Thus, targets of the same sRNA work in a concerted way toward a specific goal. In addition, in the transcription-regulatory network, sRNA targets act as "multiplexor", accepting regulatory control from multiple sources and acting accordingly. Our results indicate that sRNA targeting shows different properties when compared to the proteins that form cellular networks.
机译:背景sRNA属于非编码RNA家族,范围从大约50到400个核苷酸,起着各种重要的基因调节作用。据信大多数通过与它们的靶mRNA互补而被反式调节并起作用,以抑制核糖体闭塞的翻译。尽管对它们的功能有这种了解,但尚未了解与sRNA调控有关的全局特性。在这里,我们使用大肠埃希菌中蛋白质-蛋白质相互作用和转录调控网络方面的sRNA靶标进行拓扑分析,以阐明sRNA调控和细胞控制网络之间的全球相关性。结果对sRNA靶标的网络分析表明,可以识别某些特定的网络特性。在蛋白质-蛋白质相互作用网络中,sRNA靶标倾向于占据更多的中心位置(更高的亲和力中心,p-val = 0.022)和更多的潮语(更大的聚类系数,p-val = 0.037)。相同sRNA的靶标倾向于形成网络模块(较短的特征路径长度,p-val = 0.015;更大的密度,p-val = 0.019;度内比更高,p-val = 0.009)。使用转录调节网络,sRNA靶标往往处于多重调控下(较高的度数,p-val = 0.013),而靶标通常对调节信号的传递很重要(较高的中间性,p-val = 0.012)。正如发现的蛋白质-蛋白质相互作用网络一样,受同一sRNA调控的靶标也倾向于在转录调控网络内紧密结合(密度较大,p-val = 0.036),并且它们之间的内向相互作用更大。比外向互动要高(度数比更高,p-val = 0.023)。但是,在合并了有关预测的sRNA和下游目标的信息后,结果并不是很明确,但是总体网络模块化仍然很明显。结论我们的结果表明,针对sRNA的靶向作用倾向于表现出一种聚类模式,该模式类似于在先前研究中观察到的与蛋白质-蛋白质相互作用网络相关的人类microRNA调控。即,sRNA靶标显示紧密的相互作用并形成用于蛋白质-蛋白质相互作用和转录调节网络的紧密编织的网络模块。因此,相同sRNA的靶标可以协同工作以实现特定目标。另外,在转录调节网络中,sRNA靶充当“多路复用器”,接受来自多个来源的调节控制并据此起作用。我们的结果表明,与形成细胞网络的蛋白质相比,靶向sRNA表现出不同的特性。

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