MicroRNA targets in Drosophila.
MicroRNA targets in Drosophila.
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DOI：
10.1186/gb-2003-5-1-r1
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发表时间：
2003
期刊：
影响因子：
12.3
通讯作者：
Marks DS
中科院分区：
文献类型：
--
作者：
Enright AJ;John B;Gaul U;Tuschl T;Sander C;Marks DS
提出了一种用于microRNA靶基因全基因组预测的计算方法。将该方法应用于黑腹果蝇、拟暗果蝇和冈比亚按蚊基因组，鉴定了可能由一种或多种已知microRNA调控的数百个靶基因。最近发现的microRNA（miRNA）基因和表征的前几个目标基因调控的miRNA在秀丽隐杆线虫和果蝇的阐明了一个新的网络的监管控制奠定了基础。我们提出了一个计算方法的全基因组预测的miRNA靶基因。该方法是使用已知的例子进行验证。对于每种miRNA，靶基因的选择基于三个特性：使用位置加权局部比对算法的序列互补性，RNA-RNA双链体的自由能，以及相关基因组中靶位点的保守性。应用于D.黑腹果蝇、拟暗果蝇和冈比亚按蚊的基因组鉴定了几百个可能受一种或多种已知miRNA调控的靶基因。这些潜在的靶点富含在特定发育阶段表达的基因，这些基因参与细胞命运的指定，形态发生和发育过程的协调，以及在成熟神经系统中活跃的基因。高级靶基因在转录因子中富集两倍，并且包括已知处于翻译调控下的基因。我们的研究结果再次证实了这一论点，即miRNA在建立有序发展所需的基因活性的复杂空间和时间模式方面具有重要作用，并表明在成熟生物体的功能中具有额外的作用。此外，这些结果为确定miRNA功能的定向实验指明了方向。信使RNA的3'非翻译区中的miRNA靶位点的新兴组合学使人想起DNA的启动子区中的转录调控，在调控子和靶之间具有一对多和多对一的关系。通常，一种以上的miRNA调节一种信息，表明协同翻译控制。相反，一个miRNA可能有几个靶基因，反映了靶点的多样性。作为重点实验的指南，我们提供了有关可能的靶基因及其非翻译区结合位点的详细在线信息，按miRNA或基因组织，并按匹配可能性排序。靶标预测算法是免费提供的，并且可以使用鉴定的miRNA序列应用于全基因组序列。
A computational method for whole-genome prediction of microRNA target genes is presented. Application of this method to the Drosophila melanogaster, Drosophila pseudoobscura and Anopheles gambiae genomes identifies several hundred target genes potentially regulated by one or more known microRNAs. The recent discoveries of microRNA (miRNA) genes and characterization of the first few target genes regulated by miRNAs in Caenorhabditis elegans and Drosophila melanogaster have set the stage for elucidation of a novel network of regulatory control. We present a computational method for whole-genome prediction of miRNA target genes. The method is validated using known examples. For each miRNA, target genes are selected on the basis of three properties: sequence complementarity using a position-weighted local alignment algorithm, free energies of RNA-RNA duplexes, and conservation of target sites in related genomes. Application to the D. melanogaster, Drosophila pseudoobscura and Anopheles gambiae genomes identifies several hundred target genes potentially regulated by one or more known miRNAs. These potential targets are rich in genes that are expressed at specific developmental stages and that are involved in cell fate specification, morphogenesis and the coordination of developmental processes, as well as genes that are active in the mature nervous system. High-ranking target genes are enriched in transcription factors two-fold and include genes already known to be under translational regulation. Our results reaffirm the thesis that miRNAs have an important role in establishing the complex spatial and temporal patterns of gene activity necessary for the orderly progression of development and suggest additional roles in the function of the mature organism. In addition the results point the way to directed experiments to determine miRNA functions. The emerging combinatorics of miRNA target sites in the 3' untranslated regions of messenger RNAs are reminiscent of transcriptional regulation in promoter regions of DNA, with both one-to-many and many-to-one relationships between regulator and target. Typically, more than one miRNA regulates one message, indicative of cooperative translational control. Conversely, one miRNA may have several target genes, reflecting target multiplicity. As a guide to focused experiments, we provide detailed online information about likely target genes and binding sites in their untranslated regions, organized by miRNA or by gene and ranked by likelihood of match. The target prediction algorithm is freely available and can be applied to whole genome sequences using identified miRNA sequences.