CIRCpedia v2: An Updated Database for Comprehensive Circular RNA Annotation and Expression Comparison

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.

[1]  Ling-Ling Chen,et al.  Complementary Sequence-Mediated Exon Circularization , 2014, Cell.

[2]  Kathleen R. Cho,et al.  Scrambled exons , 1991, Cell.

[3]  Yan Li,et al.  circRNADb: A comprehensive database for human circular RNAs with protein-coding annotations , 2016, Scientific Reports.

[4]  Petar Glažar,et al.  Circular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed. , 2015, Molecular cell.

[5]  Xiang Li,et al.  The Biogenesis, Functions, and Challenges of Circular RNAs. , 2018, Molecular cell.

[6]  J. Kjems,et al.  Comparison of circular RNA prediction tools , 2015, Nucleic acids research.

[7]  N. Rajewsky,et al.  circRNA biogenesis competes with pre-mRNA splicing. , 2014, Molecular cell.

[8]  C. Cocquerelle,et al.  Splicing with inverted order of exons occurs proximal to large introns. , 1992, The EMBO journal.

[9]  Li Yang,et al.  Regulation of circRNA biogenesis , 2015, RNA biology.

[10]  Fangqing Zhao,et al.  Computational Strategies for Exploring Circular RNAs. , 2018, Trends in genetics : TIG.

[11]  Yang Wang,et al.  Efficient backsplicing produces translatable circular mRNAs , 2015, RNA.

[12]  D. Bartel,et al.  Expanded identification and characterization of mammalian circular RNAs , 2014, Genome Biology.

[13]  Li Yang,et al.  Coordinated circRNA Biogenesis and Function with NF90/NF110 in Viral Infection. , 2017, Molecular cell.

[14]  E. Schuman,et al.  Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity , 2015, Nature Neuroscience.

[15]  Michael K. Slevin,et al.  Circular RNAs are abundant, conserved, and associated with ALU repeats. , 2013, RNA.

[16]  C. Cocquerelle,et al.  Mis‐splicing yields circular RNA molecules , 1993, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[17]  Peter Goodfellow,et al.  Circular transcripts of the testis-determining gene Sry in adult mouse testis , 1993, Cell.

[18]  Dongming Liang,et al.  Short intronic repeat sequences facilitate circular RNA production , 2014, Genes & development.

[19]  Sebastian D. Mackowiak,et al.  Circular RNAs are a large class of animal RNAs with regulatory potency , 2013, Nature.

[20]  Ling-Ling Chen The biogenesis and emerging roles of circular RNAs , 2016, Nature Reviews Molecular Cell Biology.

[21]  J. Kjems,et al.  Natural RNA circles function as efficient microRNA sponges , 2013, Nature.

[22]  Charles Gawad,et al.  Circular RNAs Are the Predominant Transcript Isoform from Hundreds of Human Genes in Diverse Cell Types , 2012, PloS one.

[23]  M. Garcia-Blanco,et al.  Exon circularization in mammalian nuclear extracts. , 1996, RNA.

[24]  Tim Schneider,et al.  Exon circularization requires canonical splice signals. , 2015, Cell reports.

[25]  Andreas W. Schreiber,et al.  The RNA Binding Protein Quaking Regulates Formation of circRNAs , 2015, Cell.

[26]  G. Shan,et al.  Exon-intron circular RNAs regulate transcription in the nucleus , 2015, Nature Structural &Molecular Biology.

[27]  Li Yang,et al.  Increased complexity of circRNA expression during species evolution , 2017, RNA biology.

[28]  Howard Y. Chang,et al.  Sensing Self and Foreign Circular RNAs by Intron Identity. , 2017, Molecular cell.

[29]  Li Yang Splicing noncoding RNAs from the inside out , 2015, Wiley interdisciplinary reviews. RNA.

[30]  Li Yang,et al.  The Biogenesis of Nascent Circular RNAs. , 2016, Cell reports.

[31]  Sol Shenker,et al.  Genome-wide analysis of drosophila circular RNAs reveals their structural and sequence properties and age-dependent neural accumulation. , 2014, Cell reports.

[32]  Julia Salzman,et al.  Cell-Type Specific Features of Circular RNA Expression , 2013, PLoS genetics.

[33]  Petar Glažar,et al.  circBase: a database for circular RNAs , 2014, RNA.

[34]  Christoph Dieterich,et al.  Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. , 2015, Cell reports.

[35]  Jun Zhang,et al.  Diverse alternative back-splicing and alternative splicing landscape of circular RNAs , 2016, Genome research.

[36]  Dongming Liang,et al.  The Output of Protein-Coding Genes Shifts to Circular RNAs When the Pre-mRNA Processing Machinery Is Limiting. , 2017, Molecular cell.

[37]  Derek Y. Chiang,et al.  MapSplice: Accurate mapping of RNA-seq reads for splice junction discovery , 2010, Nucleic acids research.

[38]  Yang Gao,et al.  CSCD: a database for cancer-specific circular RNAs , 2017, Nucleic Acids Res..

[39]  Yi Zheng,et al.  Comprehensive identification of internal structure and alternative splicing events in circular RNAs , 2016, Nature Communications.

[40]  J. Wilusz,et al.  A 360° view of circular RNAs: From biogenesis to functions , 2018, Wiley interdisciplinary reviews. RNA.