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a catalog of worldwide biological databases

Recent advances on genome-wide profiling and characterization of circular RNAs have suggested their versatile roles in diverse biological processes, yet systematic elucidation of their molecular characteristics and functional mechanisms remains challenging. Here, we introduce CIRCpedia v3 (https://bits.fudan.edu.cn/circpediav3), an expanded repository to annotate both circular RNAs from back-splicing of exons (circRNAs) and circular RNAs from intron lariats (ciRNAs) by profiling 2413 sequencing datasets across 20 species. Building upon the previous version of CIRCpedia, this release identifies >2 million circular RNAs and introduces transformative advances to facilitate circular RNA research: (i) community-recommended nomenclature with enhanced molecular profiling, enabling quantitative comparison of circular/linear isoform dynamics; (ii) an interactive platform with real-time comparative analyses of circRNAs and visualizations; and (iii) integrated toolkits to identify base-editable sites, predict circRNA subcellular localization, detect circRNA degradation signals for stability optimization, predict m6A modification sites, assess circRNA coding potential, and design divergent polymerase chain reaction primers and small interfering RNAs (siRNAs). By integrating insights from cross-species expression, molecular characterization, and functional predictions, CIRCpedia v3 empowers researchers to prioritize context-specific circular RNA candidates in biological or disease conditions and to accelerate mechanistic discovery and therapeutic development.

Circular RNAs (circRNAs) from back-splicing of exon(s) have been recently identified to be broadly expressed in eukaryotes, in tissue- and species-specific manners. Although functions of most circRNAs remain elusive, some circRNAs are shown to be functional in gene expression regulation and potentially relate to diseases. Due to their stability, circRNAs can also be used as biomarkers for diagnosis. Profiling circRNAs by integrating their expression among different samples thus provides molecular basis for further functional study of circRNAs and their potential application in clinic. Here, we report CIRCpedia v2, an updated database for comprehensive circRNA annotation from over 180 RNA-seq datasets across six different species. This atlas allows users to search, browse, and download circRNAs with expression features in various cell types/tissues, including disease samples. In addition, the updated database incorporates conservation analysis of circRNAs between humans and mice. Finally, the web interface also contains computational tools to compare circRNA expression among samples. CIRCpedia v2 is accessible at http://www.picb.ac.cn/rnomics/circpedia.

Circular RNAs (circRNAs) derived from back-spliced exons have been widely identified as being co-expressed with their linear counterparts. A single gene locus can produce multiple circRNAs through alternative back-splice site selection and/or alternative splice site selection; however, a detailed map of alternative back-splicing/splicing in circRNAs is lacking. Here, with the upgraded CIRCexplorer2 pipeline, we systematically annotated different types of alternative back-splicing and alternative splicing events in circRNAs from various cell lines. Compared with their linear cognate RNAs, circRNAs exhibited distinct patterns of alternative back-splicing and alternative splicing. Alternative back-splice site selection was correlated with the competition of putative RNA pairs across introns that bracket alternative back-splice sites. In addition, all four basic types of alternative splicing that have been identified in the (linear) mRNA process were found within circRNAs, and many exons were predominantly spliced in circRNAs. Unexpectedly, thousands of previously unannotated exons were detected in circRNAs from the examined cell lines. Although these novel exons had similar splice site strength, they were much less conserved than known exons in sequences. Finally, both alternative back-splicing and circRNA-predominant alternative splicing were highly diverse among the examined cell lines. All of the identified alternative back-splicing and alternative splicing in circRNAs are available in the CIRCpedia database (http://www.picb.ac.cn/rnomics/circpedia). Collectively, the annotation of alternative back-splicing and alternative splicing in circRNAs provides a valuable resource for depicting the complexity of circRNA biogenesis and for studying the potential functions of circRNAs in different cells.