Expanded Expression Landscape and Prioritization of Circular RNAs in Mammals

• Published in: Cell reports (Cambridge) Vol. 26; no. 12; pp. 3444 - 3460.e5
• Main Authors: Ji, Peifeng, Wu, Wanying, Chen, Shuai, Zheng, Yi, Zhou, Lin, Zhang, Jinyang, Cheng, Hao, Yan, Jin, Zhang, Shaogeng, Yang, Penghui, Zhao, Fangqing
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.03.2019; Elsevier
• Subjects: Animals; circRNA; circular RNA; co-expression network; functional prioritization; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; HeLa Cells; Hep G2 Cells; High-Throughput Nucleotide Sequencing; Humans; Macaca; Mice; noncoding RNA; RNA, Circular - biosynthesis; RNA, Circular - genetics; RNA-binding protein; transcriptome; RNA-binding protein; noncoding RNA; circRNA; circular RNA; transcriptome; functional prioritization; co-expression network
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2019.02.078

Circular RNAs (circRNAs) are emerging as essential regulators of various biological and disease processes. To comprehensively understand the diversity of circRNAs and prioritize their importance, we present a large-scale study of circRNA repertoires from multiple tissues from human, macaque, and mouse. We discovered totals of 104,388, 96,675, and 82,321 circRNAs from the three species, respectively, with an average of 72.6% being successfully assembled into full-length transcripts for each species. Using these full-length circRNAs, we identified thousands of evolutionarily conserved circRNAs that were valuable for functional screening and prioritization. By constructing both species-specific and conserved gene co-expression networks, we inferred circRNA functions on a global scale and prioritized promising functional candidates. To illustrate how well-established prior knowledge facilitates to screen functional candidates, we used the circRNA co-expression networks to prioritize circRNAs that may be involved in liver tumorigenesis and experimentally validated their functions. [Display omitted] •RNA-seq libraries and data from 44 normal tissues of human, macaque, and mouse•CircAtlas is the most comprehensive catalog of circRNAs from normal tissues•72.6% of circRNAs have been assembled into full-length circular transcripts•Prioritized a new subset of circRNAs, overlapped orthologous circRNAs Ji et al. present a large-scale study of circRNA repertoires from multiple tissues of human, macaque, and mouse and propose a new approach to annotate and prioritize functional circRNAs.