GSE97382
Discovering the interactions between circRNAs and RNA-binding proteins from RNA-seq and CLIP-seq data
Although tens of thousands of circular RNAs (circRNAs) have been identified in mammalian genomes, only a few have been functionally characterized. Here, we report a new approach, circScan, to identify regulatory interactions between circRNAs and RNA-binding proteins (RBPs). Our method identifies back-splicing reads from crosslinking and immunoprecipitation followed by high-throughput sequencing (CLIP-seq) data. Using our method, we systematically scanned ~1,500 CLIP-seq datasets and identified ~12,540 and ~1,090 novel circRNA-RBP interactions in the human and mouse genomes, respectively, including all known interactions between circRNAs and Argonaute (AGO) proteins. Furthermore, more than twenty novel interactions were experimentally confirmed by RNA immunoprecipitation combined with quantitative PCR (RIP-qPCR). Importantly, we determined that natural circRNAs interact with the cap-independent translation factors eukaryotic initiation factor 3 (eIF3) and N6-methyladenosine (m6A), thus suggesting that those circRNAs may be translated into proteins. These findings demonstrate that circRNAs are regulated by various RBPs and therefore may play important roles in diverse biological processes. Overall design: Discovery of circular RNAs in 2 cell types.