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Lewis, BP; Shih, IH; Jones-Rhoades, MW; Bartel, DP; Burge, CBCell  2003,115(7)787-798 引用次数 1305

这篇发表于2003年的Cell paper截至2011年8月15日引用次数已达1305次。该文章首次成功地大规模预测了哺乳动物miRNA的靶基因。

【摘要】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.

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