Distance constraints between microRNA target sites dictate efficacy and cooperativity.
Distance constraints between microRNA target sites dictate efficacy and cooperativity.
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DOI：
10.1093/nar/gkm133
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发表时间：
2007
影响因子：
14.9
通讯作者：
Rossi JJ
中科院分区：
文献类型：
--
作者：
Saetrom P;Heale BS;Snøve O Jr;Aagaard L;Alluin J;Rossi JJ
microRNAs（miRNAs）具有调节数千个基因表达的潜力，但决定基因是否被靶向的机制知之甚少。我们研究了相同miRNA种子对之间距离的基因组分布，发现种子起始之间的中等距离大于约13 nt的倾向。实验数据显示，当两个种子位点相隔13和35 nt时，获得最佳下调。通过分析内源性miRNA和转染的小干扰RNA（siRNA）的种子位点之间的距离，我们还发现，在最佳范围内分离的位点的合作靶向可以解释文献中报道的一些siRNA脱靶效应。
MicroRNAs (miRNAs) have the potential to regulate the expression of thousands of genes, but the mechanisms that determine whether a gene is targeted or not are poorly understood. We studied the genomic distribution of distances between pairs of identical miRNA seeds and found a propensity for moderate distances greater than about 13 nt between seed starts. Experimental data show that optimal down-regulation is obtained when two seed sites are separated by between 13 and 35 nt. By analyzing the distance between seed sites of endogenous miRNAs and transfected small interfering RNAs (siRNAs), we also find that cooperative targeting of sites with a separation in the optimal range can explain some of the siRNA off-target effects that have been reported in the literature.
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