MicroRNA target prediction by expression analysis of host genes
MicroRNA target prediction by expression analysis of host genes
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DOI：
10.1101/gr.084129.108
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发表时间：
2009-03-01
期刊：
影响因子：
7
通讯作者：
Banfi, Sandro
中科院分区：
文献类型：
--
作者：
Gennarino, Vincenzo Alessandro;Sardiello, Marco;Banfi, Sandro
MicroRNAs(MiRNAs)是一种小的非编码RNA，通过诱导RNA切割或翻译抑制来控制基因的表达。大多数人类miRNAs是基因内的，作为其宿主转录单位的一部分进行转录。我们假设miRNA宿主基因及其靶基因的表达谱是负相关的，并设计了一种新的程序HOCTAR(宿主基因相对相关靶基因)，该方法根据预测的miRNA靶基因相对于各自miRNA宿主基因的反相关表达行为对预测的miRNA靶基因进行排序。HOCTAR是第一个系统预测miRNA靶标的工具，它利用同一套微阵列实验来监测miRNAs(通过其宿主基因)和候选靶标的表达。我们将该方法应用于178个人类基因内miRNA，发现它在精确定位先前验证的miRNA靶标方面比目前可用的预测软件表现得更好。高分HOCTAR预测的目标在基因本体论类别中得到了丰富，这与之前发表的数据一致，如miR-106b和miR-93。通过过表达和功能丧失分析，我们还证明了HOCTAR在预测新的miRNA靶点方面是有效的，并通过微阵列和qRT-PCR程序分别为miR-26b和miR-98鉴定了34和28个新靶点。总体而言，我们认为，与仅基于靶序列识别的程序相比，HOCTAR的使用显著减少了待测试的候选miRNA靶标的数量。最后，我们的数据进一步证实，miRNAs对大多数靶标的mRNA水平有显著影响。
MicroRNAs (miRNAs) are small noncoding RNAs that control gene expression by inducing RNA cleavage or translational inhibition. Most human miRNAs are intragenic and are transcribed as part of their hosting transcription units. We hypothesized that the expression profiles of miRNA host genes and of their targets are inversely correlated and devised a novel procedure, HOCTAR (host gene oppositely correlated targets), which ranks predicted miRNA target genes based on their anti-correlated expression behavior relative to their respective miRNA host genes. HOCTAR is the first tool for systematic miRNA target prediction that utilizes the same set of microarray experiments to monitor the expression of both miRNAs (through their host genes) and candidate targets. We applied the procedure to 178 human intragenic miRNAs and found that it performs better than currently available prediction softwares in pinpointing previously validated miRNA targets. The high-scoring HOCTAR predicted targets were enriched in Gene Ontology categories, which were consistent with previously published data, as in the case of miR-106b and miR-93. By means of overexpression and loss-of-function assays, we also demonstrated that HOCTAR is efficient in predicting novel miRNA targets and we identified, by microarray and qRT-PCR procedures, 34 and 28 novel targets for miR-26b and miR-98, respectively. Overall, we believe that the use of HOCTAR significantly reduces the number of candidate miRNA targets to be tested compared to the procedures based solely on target sequence recognition. Finally, our data further confirm that miRNAs have a significant impact on the mRNA levels of most of their targets.