Prediction of mammalian microRNA targets

Prediction of mammalian microRNA targets
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DOI:
10.1016/s0092-8674(03)01018-3
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发表时间:
2003-12-26
期刊:
影响因子:
64.5
通讯作者:
Burge, CB
Burge, CB
中科院分区:
生物学1区
文献类型:
--
作者:
Lewis, BP;Shih, IH;Burge, CB

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microRNA(miRNA)可以通过基础对mRNA的基础,昆虫和植物在MRNA中发挥重要的基因调节作用,以指定这些信息的转录后抑制。但是,脊椎动物miRNA调节的mRNA都是未知的。在这里,我们通过鉴定与miRNA的5'区域的mRNA来预测保守脊椎动物miRNA的400多个调节靶基因,并评估这些互补位点的数量和质量。使用洗牌miRNA控件进行严格的测试支持了大多数这些预测,其中误报量的比例估计为人类,小鼠和大鼠鉴定的靶标为31%,而在pufferfish和哺乳动物中鉴定出的靶标为22%。使用HeLa细胞报告基因系统对11个预测的靶标(在经过15个测试中)得到了支持。哺乳动物miRNA的预测调节靶标被富含参与转录调控的基因,但也包括出乎意料的其他功能。
MicroRNAs (miRNAs) can play important gene regulatory roles in nematodes, insects, and plants by base-pairing to mRNAs to specify posttranscriptional repression of these messages. However, the mRNAs regulated by vertebrate miRNAs are all unknown. Here we predict more than 400 regulatory target genes for the conserved vertebrate miRNAs by identifying mRNAs with conserved pairing to the 5' region of the miRNA and evaluating the number and quality of these complementary sites. Rigorous tests using shuffled miRNA controls supported a majority of these predictions, with the fraction of false positives estimated at 31% for targets identified in human, mouse, and rat and 22% for targets identified in pufferfish as well as mammals. Eleven predicted targets (out of 15 tested) were supported experimentally using a HeLa cell reporter system. The predicted regulatory targets of mammalian miRNAs were enriched for genes involved in transcriptional regulation but also encompassed an unexpectedly broad range of other functions.