The characterization of microRNA-mediated gene regulation as impacted by both target site location and seed match type.
The characterization of microRNA-mediated gene regulation as impacted by both target site location and seed match type.
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DOI：
10.1371/journal.pone.0108260
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Xu W;Wang Z;Liu Y
MicroRNAs(MiRNAs)是在基因调控和翻译抑制中发挥重要作用的小RNA分子。近年来，促进miRNA靶结合和识别的机制得到了广泛的研究。然而，miRNA靶点的位置和侧翼序列是如何影响miRNA调控的，目前还不清楚。在这项研究中，我们系统地量化了广泛的靶点在miRNA介导的基因表达调控中的作用。我们研究了位于四个不同基因区域的靶点，包括3‘非翻译区、编码序列、5’非翻译区和启动子区域。我们还在规范种子匹配的基础上引入了另外四种非规范类型的种子匹配，并将它们包括在我们的研究中。对定量蛋白质组数据的计算分析表明，位于不同区域的靶点对miRNA介导的抑制的影响不同，但具有协同作用。此外，我们还展示了非正则种子匹配和正则种子匹配之间的协同效应，从而增强了miRNA的调控效果。对靶区附近的位点可及性和mRNA序列的二级结构的进一步系统分析表明，不同位置和不同类型的种子匹配的靶点之间存在很大差异，这表明mRNA二级结构可以解释这些不同靶点影响的miRNA调控效应的一些差异。我们的研究表明，当靶点在它们的位置和包含的种子匹配类型不同时，miRNAs可能在不同的机制下调节它们的靶标。
MicroRNAs (miRNAs) are small RNA molecules that play important roles in gene regulation and translational repression. The mechanisms that facilitate miRNA target binding and recognition have been extensively studied in recent years. However, it is still not well known how the miRNA regulation is affected by the location and the flanking sequences of miRNA target sites. In this study, we systematically quantify the contribution of a wide spectrum of target sites on miRNA-mediated gene expression regulation. Our study investigates target sites located in four different gene regions, including 3' untranslated regions, coding sequences, 5′ untranslated regions and promoter regions. We have also introduced four additional non-canonical types of seed matches beyond the canonical seed matches, and included them in our study. Computational analysis of quantitative proteomic data has demonstrated that target sites located in different regions impact the miRNA-mediated repression differently but synergistically. In addition, we have shown the synergistic effects among non-canonical seed matches and canonical ones that enhance the miRNA regulatory effects. Further systematic analysis on the site accessibility near the target regions and the secondary structure of the mRNA sequences have demonstrated substantial variations among target sites of different locations and of different types of seed matches, suggesting the mRNA secondary structure could explain some of the difference in the miRNA regulatory effects impacted by these different target sites. Our study implies miRNAs might regulate their targets under different mechanisms when target sites vary in both their locations and the types of seed matches they contain.
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影响因子：
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作者：
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