RBPvsMIR: A Computational Pipeline to Identify Competing miRNAs and RNA-Binding Protein Pairs Regulating the Shared Transcripts.

Xing Zhao,Danze Chen,Jianzhen Xu,Fan Zhang,Yujie Cai

doi:10.3390/genes9090426

Xing Zhao, Danze Chen + Show 3 more

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https://doi.org/10.3390/genes9090426

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Journal: Genes	Publication Date: Aug 22, 2018
Citations: 8	License type: CC BY 4.0

Affiliation: Shantou University, Shantou University Medical College

Abstract

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.

Highlights

Gene post-transcription regulation involves several critical regulators such as microRNAs and RNA-binding proteins (RBPs). miRNAs are short non-coding RNAs that can induce transcript cleavage or protein translation repression by binding to target sites [1]. miRNAs are found to be important in a variety of cellular processes and diseases [2,3]
For an arbitrary RNA sequence, the RBPvsMIR pipeline processes it in two stages. (I) During the scanning stage, the miRNAs binding sites were searched by PITA and/or
RBPvsMIR first uses PITA/TargetScan and RBPmap algorithms to respectively scan for miRNA and RBP motifs along any query RNA sequence

Summary

Introduction

Gene post-transcription regulation involves several critical regulators such as microRNAs (miRNAs) and RNA-binding proteins (RBPs). miRNAs are short non-coding RNAs that can induce transcript cleavage or protein translation repression by binding to target sites [1]. miRNAs are found to be important in a variety of cellular processes and diseases [2,3]. Gene post-transcription regulation involves several critical regulators such as microRNAs (miRNAs) and RNA-binding proteins (RBPs). MiRNAs are short non-coding RNAs that can induce transcript cleavage or protein translation repression by binding to target sites [1]. Tominaga et al showed that nucleolin expression is modulated by both the translation-promoting protein HuR and the decay-promoting miR-494. They found that miR-494 and RBP HuR functionally competed for the modulation of nucleolin [6]. Another group of investigators found extensive competition

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