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MiRBooking模拟了微小RNA的化学计量作用模式。

MiRBooking simulates the stoichiometric mode of action of microRNAs.

作者信息

Weill Nathanaël, Lisi Véronique, Scott Nicolas, Dallaire Paul, Pelloux Julie, Major François

机构信息

Institute for Research in Immunology and Cancer, and Department of Computer Science and Operations Research, Université de Montréal, PO Box 6128, Downtown Station, Montréal, Québec H3C 3J7, Canada.

Institute for Research in Immunology and Cancer, and Department of Computer Science and Operations Research, Université de Montréal, PO Box 6128, Downtown Station, Montréal, Québec H3C 3J7, Canada

出版信息

Nucleic Acids Res. 2015 Aug 18;43(14):6730-8. doi: 10.1093/nar/gkv619. Epub 2015 Jun 18.

Abstract

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.

摘要

在真核生物中,基因表达受微小RNA(miRNA)调控,miRNA与信使RNA(mRNA)结合,通过促进其降解或诱导其抑制来干扰mRNA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,例如在mRNA水平上使用微阵列和RNA测序,或在蛋白质水平上使用荧光素酶报告基因检测和稳定同位素标记氨基酸法(SILAC)的变体。另外,计算预测也会带来明显的好处。然而,尚未有人提出针对此任务的算法。在此,我们引入一种新算法,用于根据初始转录组丰度预测全基因组表达数据。该算法模拟在给定细胞条件下发生的miRNA与mRNA杂交竞争,并推导出处于平衡状态的整套miRNA::mRNA相互作用(微靶标组)。有趣的是,解决这种竞争提高了miRNA靶标预测的准确性。此外,该模型实现了微靶标组先前报道的一个基本特性:miRNA与mRNA之间的结合不仅取决于它们的序列互补性,还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在各自丰度下的化学计量。该模型推广了先前观察到的并被描述为海绵和竞争性内源RNA的miRNA诱导的同步沉默。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0f9/4538818/0b32cec43aeb/gkv619fig1.jpg

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