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首页> 外文期刊>日本磁気共鳴医学会雑誌 >Endogenous miRNA and Target Concentrations Determine Susceptibility to Potential ceRNA Competition
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Endogenous miRNA and Target Concentrations Determine Susceptibility to Potential ceRNA Competition

机译：内源性miRNA和靶标浓度决定了潜在ceRNA竞争的敏感性

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Target competition (ceRNA crosstalk) within miRNA-regulated gene networks has been proposed to influence biological systems. To assess target competition, we characterize and quantitate miRNA networks in two cell types. Argonaute iCLIP reveals that hierarchical binding of high- to low-affinity miRNA targets is a key characteristic of in vivo activity. Quantification of cellular miRNA and mRNAcRNA target pool levels indicates that miRNA:target pool ratios and an affinity partitioned target pool accurately predict in vivo Ago binding profiles and miRNA susceptibility to target competition. Using single-cell reporters, we directly test predictions and estimate that ~3,000 additional high-affinity target sites can affect active miRNA families with low endogenous miRNA:target ratios, such as miR-92/25. In contrast, the highly expressed miR-294 and let-7 families are not susceptible to increases of nearly 10,000 sites. These results show differential susceptibility based on endogenous miRNA:target pool ratios and provide a physiological context for ceRNA competition in vivo.
机译：已提出在miRNA调控的基因网络中进行靶竞争（ceRNA串扰）以影响生物系统。为了评估靶标竞争，我们表征和定量了两种细胞类型中的miRNA网络。 Argonaute iCLIP揭示了高亲和力和低亲和力miRNA靶标的层次结合是体内活性的关键特征。定量细胞miRNA和mRNA / ncRNA目标库的水平表明，miRNA：目标库的比率和亲和力分配的目标库可准确预测体内Ago结合情况和miRNA对目标竞争的敏感性。我们使用单细胞报告基因直接测试预测结果，并估计约3,000个其他高亲和力靶位点可以影响具有低内源性miRNA：靶标比率（例如miR-92 / 25）的活性miRNA家族。相反，高表达的miR-294和let-7家族不易增加近10,000个位点。这些结果显示了基于内源性miRNA：靶标池比率的不同敏感性，并为体内ceRNA竞争提供了生理环境。

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