A pattern-based method for the identification of microRNA binding sites and their corresponding heteroduplexes

A pattern-based method for the identification of microRNA binding sites and their corresponding heteroduplexes
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DOI:
10.1016/j.cell.2006.07.031
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发表时间:
2006-09-22
期刊:
影响因子:
64.5
通讯作者:
Rigoutsos, Isidore
Rigoutsos, Isidore
中科院分区:
生物学1区
文献类型:
--
作者:
Miranda, Kevin C.;Huynh, Tien;Rigoutsos, Isidore

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我们提出了rna 22,一种用于识别microRNA结合位点及其相应的异源双链体的方法。Rna 22不依赖于跨物种保守性,对噪音具有弹性,并且与之前的方法不同,它首先在感兴趣的序列中找到推定的微小RNA结合位点,然后识别靶向微小RNA。通过计算,我们发现rna 22可以识别大多数目前已知的异源双链体。在实验上,荧光素酶测定,我们证明了30%或以上的平均抑制168的226个测试的目标。分析表明,一些microRNA可能有多达几千个靶标,并且在四个模型基因组中,74%至92%的基因转录物可能通过其非翻译区和氨基酸编码区受到microRNA的控制。我们还将该方法的关键思想扩展到低错误的microRNA前体发现方案;我们的研究表明,哺乳动物基因组中microRNA前体的数量可能在数万个范围内。
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.