A systematic screen reveals MicroRNA clusters that significantly regulate four major signaling pathways.
A systematic screen reveals MicroRNA clusters that significantly regulate four major signaling pathways.
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系统筛选揭示显着调节四种主要信号通路的 MicroRNA 簇
DOI：
10.1371/journal.pone.0048474
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Becker LE;Lu Z;Chen W;Xiong W;Kong M;Li Y
微小RNA（miRNA）在基因组中编码为单个miRNA基因或转录为多顺反子单位的基因簇。大约50%的miRNAs与相邻的miRNAs共表达。最近的研究已经开始从进化和功能的角度阐明miRNA聚类的重要性。许多miRNA簇协调调节细胞信号通路或蛋白质相互作用网络的多个成员。这种协同的靶向方法可以对整个过程产生影响，这种影响比通常与单个miRNA调控相关的较小影响要显著得多。在这项研究中，我们筛选了366个人类miRNA小基因，以确定它们对AP-1，NF-κB，c-Myc或p53转录活性的主要信号通路的影响。通过将这些数据分层到miRNA簇中，该系统性筛选为成簇的miRNA对这些信号通路的组合作用提供了实验证据。我们还验证了p53是miR-200 a的直接靶点。这项研究首次提供了miRNA簇对细胞通路影响的全景图。
MicroRNAs (miRNAs) are encoded in the genome as individual miRNA genes or as gene clusters transcribed as polycistronic units. About 50% of all miRNAs are estimated to be co-expressed with neighboring miRNAs. Recent studies have begun to illuminate the importance of the clustering of miRNAs from an evolutionary, as well as a functional standpoint. Many miRNA clusters coordinately regulate multiple members of cellular signaling pathways or protein interaction networks. This cooperative method of targeting could produce effects on an overall process that are much more dramatic than the smaller effects often associated with regulation by an individual miRNA. In this study, we screened 366 human miRNA minigenes to determine their effects on the major signaling pathways culminating in AP-1, NF-κB, c-Myc, or p53 transcriptional activity. By stratifying these data into miRNA clusters, this systematic screen provides experimental evidence for the combined effects of clustered miRNAs on these signaling pathways. We also verify p53 as a direct target of miR-200a. This study is the first to provide a panoramic view of miRNA clusters' effects on cellular pathways.
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影响因子：
4
作者：
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通讯作者：
Schorpp-Kistner, M
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