MiRBooking simulates the stoichiometric mode of action of microRNAs.
MiRBooking simulates the stoichiometric mode of action of microRNAs.
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DOI：
10.1093/nar/gkv619
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发表时间：
2015-08-18
影响因子：
14.9
通讯作者：
Major F
中科院分区：
文献类型：
--
作者：
Weill N;Lisi V;Scott N;Dallaire P;Pelloux J;Major F
在真核生物中，基因表达受microRNA（miRNAs）调节，其结合信使RNA（mRNA）并通过促进其降解或诱导其抑制来干扰其翻译成蛋白质。我们使用实验方法研究miRNA干扰对每个基因的影响，例如mRNA水平的微阵列和RNA-seq，或蛋白质水平的荧光素酶报告基因测定和SILAC的变化。或者，计算预测将提供明显的好处。然而，没有算法对这个任务已经提出。在这里，我们介绍了一种新的算法来预测全基因组表达数据从初始转录组丰度。该算法模拟了在给定细胞条件下发生的miRNA和mRNA杂交竞争，并推导出平衡时的整套miRNA：：mRNA相互作用（microtargetome）。有趣的是，解决竞争可以提高miRNA靶点预测的准确性。此外，该模型实现了先前报道的显微靶向切片机的基本性质：miRNA和mRNA之间的结合取决于它们的序列互补性，但也取决于细胞中表达的所有RNA的丰度，即所有miRNA位点和所有miRNA的化学计量（给定其各自的丰度）。该模型概括了先前观察到的miRNA诱导的同步沉默，并描述为海绵和竞争性内源RNA。
In eucaryotes, gene expression is regulated by microRNAs (miRNAs) which bind to messenger RNAs (mRNAs) and interfere with their translation into proteins, either by promoting their degradation or inducing their repression. We study the effect of miRNA interference on each gene using experimental methods, such as microarrays and RNA-seq at the mRNA level, or luciferase reporter assays and variations of SILAC at the protein level. Alternatively, computational predictions would provide clear benefits. However, no algorithm toward this task has ever been proposed. Here, we introduce a new algorithm to predict genome-wide expression data from initial transcriptome abundance. The algorithm simulates the miRNA and mRNA hybridization competition that occurs in given cellular conditions, and derives the whole set of miRNA::mRNA interactions at equilibrium (microtargetome). Interestingly, solving the competition improves the accuracy of miRNA target predictions. Furthermore, this model implements a previously reported and fundamental property of the microtargetome: the binding between a miRNA and a mRNA depends on their sequence complementarity, but also on the abundance of all RNAs expressed in the cell, i.e. the stoichiometry of all the miRNA sites and all the miRNAs given their respective abundance. This model generalizes the miRNA-induced synchronistic silencing previously observed, and described as sponges and competitive endogenous RNAs.