Miranda Kevin C, Huynh Tien, Tay Yvonne, Ang Yen-Sin, Tam Wai-Leong, Thomson Andrew M, Lim Bing, Rigoutsos Isidore
Bioinformatics and Pattern Discovery Group, IBM Thomas J. Watson Research Center, Yorktown Heights, P.O. Box 218, NY 10598, USA.
Cell. 2006 Sep 22;126(6):1203-17. doi: 10.1016/j.cell.2006.07.031.
We present rna22, a method for identifying microRNA binding sites and their corresponding heteroduplexes. Rna22 does not rely upon cross-species conservation, is resilient to noise, and, unlike previous methods, it first finds putative microRNA binding sites in the sequence of interest, then identifies the targeting microRNA. Computationally, we show that rna22 identifies most of the currently known heteroduplexes. Experimentally, with luciferase assays, we demonstrate average repressions of 30% or more for 168 of 226 tested targets. The analysis suggests that some microRNAs may have as many as a few thousand targets, and that between 74% and 92% of the gene transcripts in four model genomes are likely under microRNA control through their untranslated and amino acid coding regions. We also extended the method's key idea to a low-error microRNA-precursor-discovery scheme; our studies suggest that the number of microRNA precursors in mammalian genomes likely ranges in the tens of thousands.
我们介绍了rna22，一种用于识别微小RNA结合位点及其相应异源双链体的方法。rna22不依赖于跨物种保守性，对噪声具有抗性，并且与以前的方法不同，它首先在感兴趣的序列中找到假定的微小RNA结合位点，然后识别靶向微小RNA。在计算方面，我们表明rna22识别出了大多数目前已知的异源双链体。在实验方面，通过荧光素酶测定，我们证明了在226个测试靶点中的168个靶点平均抑制率达到30%或更高。分析表明，一些微小RNA可能有多达数千个靶点，并且在四个模型基因组中，74%至92%的基因转录本可能通过其非翻译区和氨基酸编码区受到微小RNA的调控。我们还将该方法的关键思想扩展到了一种低错误率的微小RNA前体发现方案；我们的研究表明，哺乳动物基因组中微小RNA前体的数量可能在数万范围内。
