RT Journal Article SR Electronic T1 Discovering the Interactions between Circular RNAs and RNA-binding Proteins from CLIP-seq Data using circScan JF bioRxiv FD Cold Spring Harbor Laboratory SP 115980 DO 10.1101/115980 A1 Bin Li A1 Xiao-Qin Zhang A1 Shu-Rong Liu A1 Shun Liu A1 Wen-Ju Sun A1 Qiao Lin A1 Yu-Xia Luo A1 Ke-Ren Zhou A1 Chen-Min Zhang A1 Ye-Ya Tan A1 Jian-Hua Yang A1 Liang-Hu Qu YR 2017 UL http://biorxiv.org/content/early/2017/03/11/115980.abstract AB Although tens of thousands of circular RNAs (circRNAs) have been identified in mammalian genomes, only few of them have been characterized with biological functions. Here, we report a new approach, circScan, to identify regulatory interactions between circRNAs and RNA-binding proteins (RBPs) by discovering back-splicing reads from Cross-Linking and Immunoprecipitation followed by high-throughput sequencing (CLIP-seq) data. By using our method, we have systematically scanned ~1500 CLIP-seq datasets, and identified ~12540 and ~1090 novel circRNA-RBP interactions in human and mouse genomes, respectively, which include all known interactions between circRNAs and Argonaute (AGO) proteins. More than twenty novel interactions were further experimentally confirmed by RNA Immunoprecipitation quantitative PCR (RIP-qPCR). Importantly, we uncovered that some natural circRNAs interacted with cap-independent translation factors eukaryotic initiation factor 3 (eIF3) and N6-Methyladenosine (m6A), indicating they can be translated into proteins. These findings demonstrate that circRNAs are regulated by various RBPs, suggesting they may play important roles in diverse biological processes.