lncRNA-miRNA相互作用的系统性转录组范围分析
Systematic transcriptome wide analysis of lncRNA-miRNA interactions
摘要：
长链非编码RNA（longnoncodingRNA，lncRNA）是近年来发现的一类非蛋白质编码RNA，作为调控分子参与多种生物学过程。关于非编码RNA类之间的调控相互作用知之甚少。最近的研究表明，lncRNA可能与其他非编码RNA（包括miRNA）相互作用，并通过相互作用调节其调节作用。我们假设长的非编码RNA可以作为一层与miRNA的调控相互作用参与。人类转录组中Argonaute靶标的基因组规模数据集的可用性促使我们重建miRNA和lncRNA之间相互作用的基因组规模网络。我们使用充分表征的实验性光活化核糖核苷增强交联和免疫沉淀（PAR-CLIP）数据集和最近公开的lncRNA全基因组注释来构建miRNA调控元件的全面转录组图谱。比较分析显示，许多miRNA可以靶向长的非编码RNA，除了编码转录本，从而参与非编码RNA类之间的调控相互作用的新层。我们还发现miRNA调节元件具有位置偏好，聚集在长非编码转录本的3 '和5'末端。我们还进一步重建了miRNA与lncRNA以及信使RNA相互作用的全基因组图谱。该分析表明非编码RNA类之间存在广泛的调控相互作用，并表明lncRNA具有新的功能作用。我们还提出了第一个转录组规模的lncRNA-miRNA相互作用的研究和第一份报告的基因组规模的重建涉及lncRNA的非编码RNA调控相互作用。
英文摘要：
Long noncoding RNAs (lncRNAs) are a recently discovered class of non-protein coding RNAs which have now increasingly been shown to be involved in a wide variety of biological processes as regulatory molecules. Little is known regarding the regulatory interactions between noncoding RNA classes. Recent reports have suggested that lncRNAs could potentially interact with other noncoding RNAs including miroRNAs (miRNAs) and modulate their regulatory role through interactions. We hypothesized that long noncoding RNAs could participate as a layer of regulatory interactions with miRNAs. The availability of genome-scale datasets for argonaute targets across human transcriptome has prompted us to reconstruct a genome-scale network of interactions between miRNAs and lncRNAs. We used well characterized experimental Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) datasets and the recent genome-wide annotations for lncRNAs in public domain to construct a comprehensive transcriptome-wide map of miRNA regulatory elements. Comparative analysis revealed many of the miRNAs could target long noncoding RNAs, apart from the coding transcripts thus participating in a novel layer of regulatory interactions between noncoding RNA classes. We also find the miRNA regulatory elements have a positional preference, clustering towards the 3' and 5' ends of the long noncoding transcripts. We also further reconstruct a genome-wide map of miRNA interactions with lncRNAs as well as messenger RNAs. This analysis suggests widespread regulatory interactions between noncoding RNAs classes and suggests a novel functional role for lncRNAs. We also present the first transcriptome scale study on lncRNA-miRNA interactions and the first report of a genome-scale reconstruction of a noncoding RNA regulatory interactome involving lncRNAs.
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