RBPvsMIR: A Computational Pipeline to Identify Competing miRNAs and RNA-Binding Protein Pairs Regulating the Shared Transcripts.
RBPvsMIR: A Computational Pipeline to Identify Competing miRNAs and RNA-Binding Protein Pairs Regulating the Shared Transcripts.
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RBPvsMIR：识别竞争性 miRNA 和调节共享转录本的 RNA 结合蛋白对的计算流程
作者：
Zhao X;Chen D;Cai Y;Zhang F;Xu J
基因转录后调控涉及几个关键调控因子，例如 microRNA (miRNA) 和 RNA 结合蛋白 (RBP)。积累的实验证据表明，miRNA 和 RBP 可以竞争性地调节共享的靶向转录本。尽管这建立了一种新颖的转录后调控机制，但目前还没有计算工具来扫描可能的竞争性 miRNA 和 RBP 对。在这里，我们开发了一种新颖的计算管道——RBPvsMIR——它使我们能够统计评估 miRNA 和 RBP 之间的竞争关系。 RBPvsMIR 首先与之前成功的 miRNA 和 RBP 基序发现应用相结合，沿着给定的 RNA 序列搜索重叠或相邻的结合位点。然后进行排列测试以选择具有显着富集的结合位点的 miRNA 和 RBP 对。例如，我们使用 RBPvsMIR 识别了长非编码 RNA (lncRNA) MALAT1 的 235 个竞争性 RBP-miRNA 对。湿实验室实验证实，剪接因子 SRSF2 与 miR-383、miR-502 和 miR-101 竞争调节食管鳞癌细胞中的 MALAT1。我们的研究还揭示了 miRNA 和 RBP 调节人类 lncRNA 的全局互斥模式。此外，我们还提供了一个方便的网络服务器（http://bmc.med.stu.edu.cn/RBPvsMIR），这应该可以加速探索调节共享靶向转录本的竞争性 miRNA 和 RBP 对。
Gene post-transcription regulation involves several critical regulators such as microRNAs (miRNAs) and RNA-binding proteins (RBPs). Accumulated experimental evidences have shown that miRNAs and RBPs can competitively regulate the shared targeting transcripts. Although this establishes a novel post-transcription regulation mechanism, there are currently no computational tools to scan for the possible competing miRNA and RBP pairs. Here, we developed a novel computational pipeline—RBPvsMIR—that enables us to statistically evaluate the competing relationship between miRNAs and RBPs. RBPvsMIR first combines with previously successful miRNAs and RBP motifs discovery applications to search for overlapping or adjacent binding sites along a given RNA sequence. Then a permutation test is performed to select the miRNA and RBP pairs with the significantly enriched binding sites. As an example, we used RBPvsMIR to identify 235 competing RBP-miRNA pairs for long non-coding RNA (lncRNA) MALAT1. Wet lab experiments verified that splicing factor SRSF2 competes with miR-383, miR-502 and miR-101 to regulate MALAT1 in esophageal squamous carcinoma cells. Our study also revealed the global mutual exclusive pattern for miRNAs and RBP to regulate human lncRNAs. In addition, we provided a convenient web server (http://bmc.med.stu.edu.cn/RBPvsMIR), which should accelerate the exploration of competing miRNAs and RBP pairs regulating the shared targeting transcripts.