StarBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data

Jun-Hao Li,Liang-Hu Qu,Jian-Hua Yang,Hui Zhou,Shun Liu

doi:10.1093/nar/gkt1248

Abstract

Although microRNAs (miRNAs), other non-coding RNAs (ncRNAs) (e.g. lncRNAs, pseudogenes and circRNAs) and competing endogenous RNAs (ceRNAs) have been implicated in cell-fate determination and in various human diseases, surprisingly little is known about the regulatory interaction networks among the multiple classes of RNAs. In this study, we developed starBase v2.0 (http://starbase.sysu.edu.cn/) to systematically identify the RNA–RNA and protein–RNA interaction networks from 108 CLIP-Seq (PAR-CLIP, HITS-CLIP, iCLIP, CLASH) data sets generated by 37 independent studies. By analyzing millions of RNA-binding protein binding sites, we identified ∼9000 miRNA-circRNA, 16 000 miRNA-pseudogene and 285 000 protein–RNA regulatory relationships. Moreover, starBase v2.0 has been updated to provide the most comprehensive CLIP-Seq experimentally supported miRNA-mRNA and miRNA-lncRNA interaction networks to date. We identified ∼10 000 ceRNA pairs from CLIP-supported miRNA target sites. By combining 13 functional genomic annotations, we developed miRFunction and ceRNAFunction web servers to predict the function of miRNAs and other ncRNAs from the miRNA-mediated regulatory networks. Finally, we developed interactive web implementations to provide visualization, analysis and downloading of the aforementioned large-scale data sets. This study will greatly expand our understanding of ncRNA functions and their coordinated regulatory networks.

Highlights

Eukaryotic genomes encode thousands of short and long non-coding RNAs, such as microRNAs, long non-coding RNAs, pseudogenes and circular RNAs
In starBase v2.0, we performed a large-scale integration of public RNA-binding proteins (RBP) binding sites generated by high-throughput CLIP-Seq technology and provided the most comprehensive RBP data set for various cell types that are presently available
By analyzing a large set of Ago and RBP binding sites derived from all available CLIP-Seq experimental techniques (PAR-CLIP, HITS-CLIP, iCLIP, CLASH), we have shown extensive and complex RNA–RNA and protein–RNA interaction networks

Summary

INTRODUCTION

Eukaryotic genomes encode thousands of short and long non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), pseudogenes and circular RNAs (circRNAs) These RNA molecules are emerging as key regulators of diverse cellular processes, including proliferation, apoptosis, differentiation and the cell cycle [1,2,3,4,5,6,7]. The understanding of ceRNA mechanisms and its consequences are in their infancy, and further experimental evidences and large-scale bioinformatic efforts for ceRNAs are needed Despite these intriguing studies of individual miRNA-ncRNA and protein–RNA interactions, generalizing these findings to thousands of RNAs remains a daunting challenge. In starBase v2.0, we performed a large-scale integration of public RBP binding sites generated by high-throughput CLIP-Seq technology and provided the most comprehensive RBP data set for various cell types that are presently available. By analyzing millions of Ago and other RBP binding sites, we constructed the most comprehensive miRNA-lncRNA, miRNA-pseudogene, miRNA-circRNA, miRNA-mRNA and protein–RNA interaction networks

MATERIALS AND METHODS

Findings

CONCLUSIONS