Brennecke Julius, Stark Alexander, Russell Robert B, Cohen Stephen M
European Molecular Biology Laboratory, Heidelberg, Germany.
PLoS Biol. 2005 Mar;3(3):e85. doi: 10.1371/journal.pbio.0030085.
MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression in plants and animals. Although their biological importance has become clear, how they recognize and regulate target genes remains less well understood. Here, we systematically evaluate the minimal requirements for functional miRNA-target duplexes in vivo and distinguish classes of target sites with different functional properties. Target sites can be grouped into two broad categories. 5' dominant sites have sufficient complementarity to the miRNA 5' end to function with little or no support from pairing to the miRNA 3' end. Indeed, sites with 3' pairing below the random noise level are functional given a strong 5' end. In contrast, 3' compensatory sites have insufficient 5' pairing and require strong 3' pairing for function. We present examples and genome-wide statistical support to show that both classes of sites are used in biologically relevant genes. We provide evidence that an average miRNA has approximately 100 target sites, indicating that miRNAs regulate a large fraction of protein-coding genes and that miRNA 3' ends are key determinants of target specificity within miRNA families.
微小RNA（miRNA）是短的非编码RNA，可调节植物和动物中的基因表达。尽管它们的生物学重要性已变得清晰，但它们如何识别和调节靶基因仍不太清楚。在这里，我们系统地评估了体内功能性miRNA-靶标双链体的最低要求，并区分了具有不同功能特性的靶位点类别。靶位点可分为两大类。5'主导位点与miRNA 5'端具有足够的互补性，在与miRNA 3'端配对很少或没有支持的情况下也能发挥作用。实际上，在5'端很强的情况下，3'端配对低于随机噪声水平的位点也具有功能。相比之下，3'补偿位点的5'端配对不足，需要很强的3'端配对才能发挥功能。我们给出了实例并提供全基因组统计支持，以表明这两类位点都在生物学相关基因中被使用。我们提供的证据表明，平均每个miRNA约有100个靶位点，这表明miRNA调节很大一部分蛋白质编码基因，并且miRNA 家族内的靶标特异性的关键决定因素是miRNA的3'端。
