Global analyses of the effect of different cellular contexts on microRNA targeting.
Global analyses of the effect of different cellular contexts on microRNA targeting.
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DOI：
10.1016/j.molcel.2014.02.013
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发表时间：
2014-03-20
期刊：
影响因子：
16
通讯作者：
Bartel, David P.
中科院分区：
文献类型：
--
作者：
Nam, Jin-Wu;Rissland, Olivia S.;Koppstein, David;Abreu-Goodger, Cei;Jan, Calvin H.;Agarwal, Vikram;Yildirim, Muhammed A.;Rodriguez, Antony;Bartel, David P.
MicroRNA调控显然影响动物的发育，但发育及其所产生的细胞环境的多样性对miRNA调控的影响程度尚未被探索。在这里，我们比较了不同细胞系和组织中由相同miRNAs抑制的基因队列，发现靶基因谱带基本上没有受到影响，次级效应解释了检测到的大多数差异反应。差异直接靶向导致的异常值通常归因于调节miRNA位点存在的替代3‘UTR异构体使用。对替代的3‘UTR亚型进行更全面的检查，发现当比较任何两种细胞类型时，它们影响~10%的预测靶点。事实上，考虑替代的3‘非编码区异构体使用大大改善了靶向疗效的预测，大大超过了考虑结构性异构体使用时所观察到的改进。因此，尽管miRNA靶向在不同类型的细胞中非常一致，但考虑到3‘UTR的情况有助于预测靶向效率，并解释观察到的差异调控。
MicroRNA regulation clearly impacts animal development, but the extent to which development—with its resulting diversity of cellular contexts—impacts miRNA regulation has not been explored. Here, we compare cohorts of genes repressed by the same miRNAs in different cell lines and tissues, and find that target repertoires were largely unaffected, with secondary effects explaining most of the differential responses detected. Outliers resulting from differential direct targeting were often attributable to alternative 3'UTR isoform usage that modulated the presence of miRNA sites. More inclusive examination of alternative 3'UTR isoforms revealed that they influence ~10% of predicted targets when comparing any two cell types. Indeed, considering alternative 3'UTR isoform usage improved prediction of targeting efficacy significantly beyond the improvements observed when considering constitutive isoform usage. Thus, although miRNA targeting is remarkably consistent in different cell types, considering the 3'UTR landscape helps predict targeting efficacy and explain differential regulation that is observed.
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