Predicting microRNA targeting efficacy in Drosophila.
Predicting microRNA targeting efficacy in Drosophila.
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DOI：
10.1186/s13059-018-1504-3
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发表时间：
2018-10-04
期刊：
影响因子：
12.3
通讯作者：
Bartel DP
中科院分区：
文献类型：
--
作者：
Agarwal V;Subtelny AO;Thiru P;Ulitsky I;Bartel DP
microRNA（miRNAs）是由发夹前体衍生的短调控RNA。对于理解miRNA的功能作用重要的是预测对每个miRNA最敏感的信使RNA（mRNA）靶标的能力。由于缺乏测量miRNA对mRNA水平影响的数据集，在果蝇和其他无脊椎动物物种中开发miRNA靶向定量模型的进展落后于哺乳动物。我们获得了适合于果蝇中miRNA靶向定量研究的数据集。对这些数据的分析扩展了已知在果蝇中有效的调控位点的类型，扩展了具有可检测靶向的mRNA区域，以包括5′非翻译区，并确定了与果蝇细胞中靶向功效相关的位点背景特征。最新的进化分析评估了每个预测位点保守靶向的概率，并表明超过三分之一的果蝇基因是miRNAs的优先保守靶点。在此基础上，建立了一个预测昆虫靶向效果的定量模型。该模型的性能优于现有模型，并且它驱动了TargetScanFly的最新版本v7。我们的进化和功能分析扩大了已知的范围，在苍蝇和其他昆虫的miRNA靶向。使用果蝇数据开发和训练的定量模型的存在将为将miRNA置于这种重要实验生物的基因调控网络中提供有价值的资源。本文的在线版本（10.1186/s13059-018-1504-3）包含补充材料，可供授权用户使用。
MicroRNAs (miRNAs) are short regulatory RNAs that derive from hairpin precursors. Important for understanding the functional roles of miRNAs is the ability to predict the messenger RNA (mRNA) targets most responsive to each miRNA. Progress towards developing quantitative models of miRNA targeting in Drosophila and other invertebrate species has lagged behind that of mammals due to the paucity of datasets measuring the effects of miRNAs on mRNA levels. We acquired datasets suitable for the quantitative study of miRNA targeting in Drosophila. Analyses of these data expanded the types of regulatory sites known to be effective in flies, expanded the mRNA regions with detectable targeting to include 5′ untranslated regions, and identified features of site context that correlate with targeting efficacy in fly cells. Updated evolutionary analyses evaluated the probability of conserved targeting for each predicted site and indicated that more than a third of the Drosophila genes are preferentially conserved targets of miRNAs. Based on these results, a quantitative model was developed to predict targeting efficacy in insects. This model performed better than existing models, and it drives the most recent version, v7, of TargetScanFly. Our evolutionary and functional analyses expand the known scope of miRNA targeting in flies and other insects. The existence of a quantitative model that has been developed and trained using Drosophila data will provide a valuable resource for placing miRNAs into gene regulatory networks of this important experimental organism. The online version of this article (10.1186/s13059-018-1504-3) contains supplementary material, which is available to authorized users.
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