Integrated network analysis reveals distinct regulatory roles of transcription factors and microRNAs.
Integrated network analysis reveals distinct regulatory roles of transcription factors and microRNAs.
复制标题
DOI：
10.1261/rna.048025.114
复制
发表时间：
2016-11
期刊：
影响因子：
--
通讯作者：
Yu H
中科院分区：
文献类型：
--
作者：
Guo Y;Alexander K;Clark AG;Grimson A;Yu H
对转录调控网络的分析揭示了控制基因表达调控的许多主要特征。 MicroRNA (miRNA) 已成为另一类在转录后影响基因表达的主要基因调控因子，但仍然需要定量评估它们在基因调控中的整体作用。在这里，我们构建了一个由转录因子（TF）、miRNA及其靶基因组成的整合基因调控网络，并分析了调控对靶mRNA表达、靶蛋白表达、蛋白质-蛋白质相互作用和疾病关联的影响。我们发现，虽然受相同 TF 调节的靶基因倾向于共表达，但 miRNA 的共调节不会导致在 mRNA 或蛋白质水平上评估的共表达。对调控网络中相互作用的蛋白质对的分析表明，与由 miRNA 共同调控的基因相比，由 TF 共同调控的基因在同一复合体中编码蛋白质的比例更高。尽管这些结果表明由 TF 共同调节的基因比由 miRNA 共同调节的基因在功能上更相关，但共享 TF 或 miRNA 调节因子的基因更有可能引起相同的疾病。对 TF 和 miRNA 之间相互作用的进一步分析表明，TF 倾向于调节模块内/通路簇，而 miRNA 倾向于调节模块间/通路簇。这些结果表明，尽管 TF 和 miRNA 都调节基因表达，但它们在细胞内的整体调节网络中占据不同的位置。
Analysis of transcription regulatory networks has revealed many principal features that govern gene expression regulation. MicroRNAs (miRNAs) have emerged as another major class of gene regulators that influence gene expression post-transcriptionally, but there remains a need to assess quantitatively their global roles in gene regulation. Here, we have constructed an integrated gene regulatory network comprised of transcription factors (TFs), miRNAs, and their target genes and analyzed the effect of regulation on target mRNA expression, target protein expression, protein–protein interaction, and disease association. We found that while target genes regulated by the same TFs tend to be co-expressed, co-regulation by miRNAs does not lead to co-expression assessed at either mRNA or protein levels. Analysis of interacting protein pairs in the regulatory network revealed that compared to genes co-regulated by miRNAs, a higher fraction of genes co-regulated by TFs encode proteins in the same complex. Although these results suggest that genes co-regulated by TFs are more functionally related than those co-regulated by miRNAs, genes that share either TF or miRNA regulators are more likely to cause the same disease. Further analysis on the interplay between TFs and miRNAs suggests that TFs tend to regulate intramodule/pathway clusters, while miRNAs tend to regulate intermodule/pathway clusters. These results demonstrate that although TFs and miRNAs both regulate gene expression, they occupy distinct niches in the overall regulatory network within the cell.
登录
查看更多内容
影响因子：
--
作者：
Das J;Yu H
通讯作者：
Yu H
影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
3.9
作者：
Amberger, Joanna;Bocchini, Carol;Hamosh, Ada
通讯作者：
Hamosh, Ada
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium
影响因子：
30.8
作者：
Chang, Tsung-Cheng;Yu, Duonan;Mendell, Joshua T.
通讯作者：
Mendell, Joshua T.