CircInteractome: a web tool for exploring circular RNAs and their interacting proteins and microRNAs

ABSTRACTCircular RNAs (circRNAs) are widely expressed in animal cells, but their biogenesis and functions are poorly understood. CircRNAs have been shown to act as sponges for miRNAs and may also potentially sponge RNA-binding proteins (RBPs) and are thus predicted to function as robust posttranscriptional regulators of gene expression. The joint analysis of large-scale transcriptome data coupled with computational analyses represents a powerful approach to elucidate possible biological roles of ribonucleoprotein (RNP) complexes. Here, we present a new web tool, CircInteractome (circRNA interactome), for mapping RBP- and miRNA-binding sites on human circRNAs. CircInteractome searches public circRNA, miRNA, and RBP databases to provide bioinformatic analyses of binding sites on circRNAs and additionally analyzes miRNA and RBP sites on junction and junction-flanking sequences. CircInteractome also allows the user the ability to (1) identify potential circRNAs which can act as RBP sponges, (2) design junction-spanning primers for specific detection of circRNAs of interest, (3) design siRNAs for circRNA silencing, and (4) identify potential internal ribosomal entry sites (IRES). In sum, the web tool CircInteractome, freely accessible at http://circinteractome.nia.nih.gov, facilitates the analysis of circRNAs and circRNP biology.

摘要
环形RNA（circRNAs, Circular RNAs）广泛表达于动物细胞中，但其生物发生机制与生物学功能目前仍未得到充分阐明。已有研究证实，环形RNA可作为微小RNA（miRNAs, microRNAs）的分子海绵发挥作用，同时也可能靶向结合RNA结合蛋白（RBPs, RNA-binding proteins），因此被预测为一类强效的基因表达转录后调控因子。大规模转录组数据分析结合计算生物学分析的联合研究策略，是阐明核糖核蛋白（RNP, ribonucleoprotein）复合物潜在生物学功能的有效手段。本研究推出一款新型网络工具——CircInteractome（环形RNA互作组），用于定位人类环形RNA上的RNA结合蛋白与微小RNA结合位点。该工具通过检索公开的环形RNA、微小RNA与RNA结合蛋白数据库，对环形RNA上的结合位点进行生物信息学分析，同时还可分析反向剪接位点及其侧翼序列上的微小RNA与RNA结合蛋白结合位点。CircInteractome支持用户完成以下四项操作：（1）筛选可作为RNA结合蛋白海绵的潜在环形RNA；（2）设计跨反向剪接位点引物，以特异性检测目标环形RNA；（3）设计用于环形RNA沉默的小干扰RNA（siRNA）；（4）预测潜在的内部核糖体进入位点（IRES, internal ribosomal entry sites）。综上，这款可通过http://circinteractome.nia.nih.gov免费访问的网络工具CircInteractome，可为环形RNA及环形核糖核蛋白（circRNP）的生物学研究提供便捷助力。