Burgler Craig, Macdonald Paul M
Section of Molecular Cell and Developmental Biology, Institute for Cell and Molecular Biology, The University of Texas at Austin, 1 University Station A-4800, Austin, TX 78712-0159, USA.
BMC Genomics. 2005 Jun 8;6:88. doi: 10.1186/1471-2164-6-88.
BACKGROUND: MicroRNAs (miRNAs) mediate a form of translational regulation in animals. Hundreds of animal miRNAs have been identified, but only a few of their targets are known. Prediction of miRNA targets for translational regulation is challenging, since the interaction with the target mRNA usually occurs via incomplete and interrupted base pairing. Moreover, the rules that govern such interactions are incompletely defined. RESULTS: MovingTargets is a software program that allows a researcher to predict a set of miRNA targets that satisfy an adjustable set of biological constraints. We used MovingTargets to identify a high-likelihood set of 83 miRNA targets in Drosophila, all of which adhere to strict biological constraints. We tested and verified 3 of these predictions in cultured cells, including a target for the Drosophila let-7 homolog. In addition, we utilized the flexibility of MovingTargets by relaxing the biological constraints to identify and validate miRNAs targeting tramtrack, a gene also known to be subject to translational control dependent on the RNA binding protein Musashi. CONCLUSION: MovingTargets is a flexible tool for the accurate prediction of miRNA targets in Drosophila. MovingTargets can be used to conduct a genome-wide search of miRNA targets using all Drosophila miRNAs and potential targets, or it can be used to conduct a focused search for miRNAs targeting a specific gene. In addition, the values for a set of biological constraints used to define a miRNA target are adjustable, allowing the software to incorporate the rules used to characterize a miRNA target as these rules are experimentally determined and interpreted.
背景：微小RNA（miRNA）介导动物体内一种形式的翻译调控。数百种动物miRNA已被鉴定出来，但仅知晓其中少数的靶标。由于与靶标mRNA的相互作用通常通过不完全且间断的碱基配对发生，因此预测用于翻译调控的miRNA靶标具有挑战性。此外，支配此类相互作用的规则尚未完全明确。 结果：MovingTargets是一款软件程序，它能让研究人员预测一组满足可调整生物约束条件的miRNA靶标。我们使用MovingTargets在果蝇中鉴定出一组83个高可能性的miRNA靶标，所有这些靶标均符合严格的生物约束条件。我们在培养细胞中测试并验证了其中3个预测结果，包括果蝇let-7同源物的一个靶标。此外，我们通过放宽生物约束条件利用MovingTargets的灵活性，以鉴定和验证靶向tramtrack的miRNA，tramtrack是一个已知也受依赖于RNA结合蛋白Musashi的翻译控制的基因。 结论：MovingTargets是用于准确预测果蝇中miRNA靶标的灵活工具。MovingTargets可用于使用所有果蝇miRNA和潜在靶标进行全基因组范围内的miRNA靶标搜索，或者可用于针对靶向特定基因的miRNA进行重点搜索。此外，用于定义miRNA靶标的一组生物约束条件的值是可调整的，这使得该软件能够纳入用于表征miRNA靶标的规则，因为这些规则是通过实验确定和解释的。
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