Systematic identification of microRNA functions by combining target prediction and expression profiling.
Systematic identification of microRNA functions by combining target prediction and expression profiling.
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DOI：
10.1093/nar/gkl068
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发表时间：
2006
影响因子：
14.9
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Wang X;Wang X
靶标预测和验证是microRNA（miRNA）研究者面临的主要障碍。动物miRNA靶标预测是具有挑战性的，因为有限的miRNA序列的互补性的目标。此外，只有少数预测的靶点得到了实验验证，并且对miRNA的机制知之甚少。在这里，我们提出了一种新的动物miRNA靶点预测算法。该算法结合了miRNA靶点识别的相关参数，并根据这些参数的相对重要性为它们分配不同的权重。引入得分计算方案以反映每个参数的强度。我们还进行了微阵列时间过程实验，以确定由于miRNA过表达下调的基因。将计算靶点预测与miRNA转染实验相结合，系统地鉴定人miR-124的基因靶点。miR-124过表达导致许多细胞周期相关基因的显著下调。这可能是在miRNA过表达的早期直接抑制少数细胞生长抑制因子的结果，这些靶基因在很长一段时间内被持续抑制。我们的高通量方法可以推广到全球范围内识别其他miRNA的靶标和功能。
Target predictions and validations are major obstacles facing microRNA (miRNA) researchers. Animal miRNA target prediction is challenging because of limited miRNA sequence complementarity to the targets. In addition, only a small number of predicted targets have been experimentally validated and the miRNA mechanism is poorly understood. Here we present a novel algorithm for animal miRNA target prediction. The algorithm combines relevant parameters for miRNA target recognition and heuristically assigns different weights to these parameters according to their relative importance. A score calculation scheme is introduced to reflect the strength of each parameter. We also performed microarray time course experiments to identify downregulated genes due to miRNA overexpression. The computational target prediction is combined with the miRNA transfection experiment to systematically identify the gene targets of human miR-124. miR-124 overexpression led to a significant downregulation of many cell cycle related genes. This may be the result of direct suppression of a few cell growth inhibitors at the early stage of miRNA overexpression, and these targeted genes were continuously suppressed over a long period of time. Our high-throughput approach can be generalized to globally identify the targets and functions of other miRNAs.
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