Toward a combinatorial nature of microRNA regulation in human cells.
Toward a combinatorial nature of microRNA regulation in human cells.
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DOI：
10.1093/nar/gks759
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发表时间：
2012-10
影响因子：
14.9
通讯作者：
Linial M
中科院分区：
文献类型：
--
作者：
Balaga O;Friedman Y;Linial M
microRNA（miRNAs）在转录后负调控信使RNA（mRNA）的水平。CLIP（交联免疫沉淀）技术的最新进展允许捕获miRNA及其同源mRNA。因此，已经发现了数千个经过验证的mRNA-miRNA对。在此，我们提出了一个全面的概述组合调控的miRNA。我们在miRror 2.0算法中实现了组合和统计约束。miRror估计了组合miRNA活性的可能性，以解释观察到的数据。我们测试了miRror在从过表达miRNA的细胞的30个转录组学谱中恢复正确的miRNA方面的成功，并从在CLIP实验中观察到的miRNA集中鉴定了数百个基因。我们表明，miRror在从过表达实验和CLIP数据中恢复miRNA调控方面的成功上级十几种领先的miRNA靶预测算法。我们进一步描述了由成对的miRNA执行的联合调节的替代模式之间的平衡。最后，对操作的细胞进行了测试，以确定miRNA是否可能参与其转录组的形成。我们确定的情况下，观察到的转录组可以解释的组合调控的miRNA对。我们的结论是，联合操作的miRNAs是一个有吸引力的策略，以维持细胞的稳态，克服了低特异性固有的个别miRNA-mRNA相互作用。
MicroRNAs (miRNAs) negatively regulate the levels of messenger RNA (mRNA) post-transcriptionally. Recent advances in CLIP (cross-linking immunoprecipitation) technology allowed capturing miRNAs with their cognate mRNAs. Consequently, thousands of validated mRNA–miRNA pairs have been revealed. Herein, we present a comprehensive outline for the combinatorial regulation by miRNAs. We implemented combinatorial and statistical constraints in the miRror2.0 algorithm. miRror estimates the likelihood of combinatorial miRNA activity in explaining the observed data. We tested the success of miRror in recovering the correct miRNA from 30 transcriptomic profiles of cells overexpressing a miRNA, and to identify hundreds of genes from miRNA sets, which are observed in CLIP experiments. We show that the success of miRror in recovering the miRNA regulation from overexpression experiments and CLIP data is superior in respect to a dozen leading miRNA-target prediction algorithms. We further described the balance between alternative modes of joint regulation that are executed by pairs of miRNAs. Finally, manipulated cells were tested for the possible involvement of miRNA in shaping their transcriptomes. We identified instances in which the observed transcriptome can be explained by a combinatorial regulation of miRNA pairs. We conclude that the joint operation of miRNAs is an attractive strategy to maintain cell homeostasis and overcoming the low specificity inherent in individual miRNA–mRNA interaction.
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影响因子：
4.3
作者：
Ivanovska, Irena;Cleary, Michele A.
通讯作者：
Cleary, Michele A.
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C
DOI：
10.1073/pnas.0803230105
发表时间：
2008-09-30
影响因子：
11.1
作者：
Forman, Joshua J.;Legesse-Miller, Aster;Coller, Hilary A.
通讯作者：
Coller, Hilary A.
影响因子：
12.3
作者：
Cloonan N;Wani S;Xu Q;Gu J;Lea K;Heater S;Barbacioru C;Steptoe AL;Martin HC;Nourbakhsh E;Krishnan K;Gardiner B;Wang X;Nones K;Steen JA;Matigian NA;Wood DL;Kassahn KS;Waddell N;Shepherd J;Lee C;Ichikawa J;McKernan K;Bramlett K;Kuersten S;Grimmond SM
通讯作者：
Grimmond SM
影响因子：
46.9
作者：
Friedlaender, Marc R.;Chen, Wei;Rajewsky, Nikolaus
通讯作者：
Rajewsky, Nikolaus