Combinatorial microRNA target predictions
Combinatorial microRNA target predictions
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DOI：
10.1038/ng1536
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发表时间：
2005-05-01
期刊：
影响因子：
30.8
通讯作者：
Rajewsky, N
中科院分区：
文献类型：
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作者：
Krek, A;Grun, D;Rajewsky, N
microRNA是小的非编码RNA，它们识别并与动物中靶基因的3'未翻译区域的部分互补位点结合，并通过未知机制调节靶转录的蛋白质产生（1-3）。不同的microRNA组合在不同的细胞类型中表达，并可能协调调节细胞特异性靶基因。在这里，我们提出了PICTAR，这是一种用于识别microRNA的常见目标的计算方法。使用八个脊椎动物基因组的全基因组比对，PICTAR专门恢复已发表的microRNA靶标的能力以及对七个预测靶标的实验验证的统计检验表明，PICTAR在预测单个microRNA的靶标和MicroRNAS组合方面具有出色的成功率。我们发现，平均而言，脊椎动物microRNA靶标每个靶标的靶标约为200个转录本。此外，我们的结果表明MicroRNA执行的广泛坐标控制。特别是，我们通过MiR-375，miR-124和Let-7b实验验证MTPN的共同调节，从而为哺乳动物中的microRNA控制提供了证据。
MicroRNAs are small noncoding RNAs that recognize and bind to partially complementary sites in the 3' untranslated regions of target genes in animals and, by unknown mechanisms, regulate protein production of the target transcript(1-3). Different combinations of microRNAs are expressed in different cell types and may coordinately regulate cell-specific target genes. Here, we present PicTar, a computational method for identifying common targets of microRNAs. Statistical tests using genome-wide alignments of eight vertebrate genomes, PicTar's ability to specifically recover published microRNA targets, and experimental validation of seven predicted targets suggest that PicTar has an excellent success rate in predicting targets for single microRNAs and for combinations of microRNAs. We find that vertebrate microRNAs target, on average, roughly 200 transcripts each. Furthermore, our results suggest widespread coordinate control executed by microRNAs. In particular, we experimentally validate common regulation of Mtpn by miR-375, miR-124 and let-7b and thus provide evidence for coordinate microRNA control in mammals.