Abstract：
MicroRNAs (miRNAs) are endogenous ~23 nt RNAs which regulate message RNA (mRNA) targets mainly through perfect pairing with their seed region (positions 2-7). Several instances of UTR sequence with an additional nucleotide that might form a bulge within the pairing region, can also be recognized by miRNA as their target (bugle-target). But the prevalence of such imperfect base pairings in human and their roles in the evolution are incompletely understood. We found that human miRNAs with the CG dinucleotides (CG dimer) in their seed region have a significant low mutation rate than their putative binding sites in mRNA targets. Interspecific comparation shows that these miRNAs had very few conservative targets with the perfect seed-pairing, while potentially having a subclass of bulge-targets. Compared with the canonical target (perfect seed-pairing), these bulge-targets had a lower negative correlation with the miRNA expression, and either were down-regulated in the miRNA overexpression experiment or up-regulated in the miRNA knock-down experiment. Our results show that the bulge-targets are widespread in the miRNAs with CG dinucleotide within their seed regions, which could in part explain the rare conserved targets of these miRNAs based on seed rule. Incorporating these bulge-targets, together with conservation information, could more accurately predict the entire targets of these miRNAs.
摘要：
MicroRNAs(miRNAs)是内源性的~23ntRNA,其主要通过与其种子区域(位置2-7)的完美配对来调节信息RNA(mRNA)靶标。UTR序列的几个实例具有可能在配对区域内形成凸起的额外核苷酸，也可以被miRNA识别为它们的靶标(喇叭-靶标)。但是，这种不完美的碱基对在人类中的普遍存在及其在进化中的作用尚未完全理解。我们发现，在其种子区域具有CG二核苷酸（CG二聚体）的人miRNA的突变率明显低于其在mRNA靶标中的推定结合位点。种间比较表明，这些miRNA具有很少的保守靶标，具有完美的种子配对，同时可能具有凸出目标的子类。与规范目标(完美种子配对)相比，这些凸起靶标与miRNA表达的负相关较低，在miRNA过表达实验中下调或在miRNA敲低实验中上调。我们的结果表明，凸起靶标在其种子区域内具有CG二核苷酸的miRNA中广泛存在，这可以部分解释基于种子规则的这些miRNA的罕见保守靶标。结合这些凸出目标，连同保护信息，可以更准确地预测这些miRNA的整个靶标。
