Circular RNAs are abundant, conserved, and associated with ALU repeats
William R. Jeck,Jessica A. Sorrentino,Kai Wang,Michael K. Slevin,Christin E. Burd,Jinze Liu,William F. Marzluff,Norman E. Sharpless +7 more
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TLDR
High-throughput sequencing of libraries prepared from ribosome-depleted RNA with or without digestion with the RNA exonuclease showed that ecircRNAs are abundant, stable, conserved and nonrandom products of RNA splicing that could be involved in control of gene expression.Abstract:
Circular RNAs composed of exonic sequence have been described in a small number of genes. Thought to result from splicing errors, circular RNA species possess no known function. To delineate the universe of endogenous circular RNAs, we performed high-throughput sequencing (RNA-seq) of libraries prepared from ribosome-depleted RNA with or without digestion with the RNA exonuclease, RNase R. We identified >25,000 distinct RNA species in human fibroblasts that contained non-colinear exons (a "backsplice") and were reproducibly enriched by exonuclease degradation of linear RNA. These RNAs were validated as circular RNA (ecircRNA), rather than linear RNA, and were more stable than associated linear mRNAs in vivo. In some cases, the abundance of circular molecules exceeded that of associated linear mRNA by >10-fold. By conservative estimate, we identified ecircRNAs from 14.4% of actively transcribed genes in human fibroblasts. Application of this method to murine testis RNA identified 69 ecircRNAs in precisely orthologous locations to human circular RNAs. Of note, paralogous kinases HIPK2 and HIPK3 produce abundant ecircRNA from their second exon in both humans and mice. Though HIPK3 circular RNAs contain an AUG translation start, it and other ecircRNAs were not bound to ribosomes. Circular RNAs could be degraded by siRNAs and, therefore, may act as competing endogenous RNAs. Bioinformatic analysis revealed shared features of circularized exons, including long bordering introns that contained complementary ALU repeats. These data show that ecircRNAs are abundant, stable, conserved and nonrandom products of RNA splicing that could be involved in control of gene expression.read more
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CircRNAs in hematopoiesis and hematological malignancies
TL;DR: Current insight in circRNA biogenesis is presented discussing the relevance for hematopoiesis of the highly interleaved processes of splicing and circ RNA biogenesis, and circRNAs high and regulated expression in blood cell types indicate that further studies are warranted to inform the position of these regulators in normal and malignant hematopoliesis.
Journal ArticleDOI
circFBXW7 Inhibits Malignant Progression by Sponging miR-197-3p and Encoding a 185-aa Protein in Triple-Negative Breast Cancer.
Feng Ye,Guanfeng Gao,Yutian Zou,Shaoquan Zheng,Lijuan Zhang,Xueqi Ou,Xiaoming Xie,Hailin Tang +7 more
TL;DR: It is demonstrated that circFBXW7 sponges miR-197-3p and encodes the FBXw7-185aa protein to suppress TNBC progression through upregulating FBXW8 expression, which may act as a therapeutic target and prognostic biomarker for TNBC.
Journal ArticleDOI
Circular RNAs as Therapeutic Agents and Targets.
TL;DR: Reports, where manipulating circRNA abundance has been shown to have therapeutic value in animal disease models in vivo, are described, with a focus on cardiovascular disease (CVD).
Journal ArticleDOI
The bioinformatics toolbox for circRNA discovery and analysis.
TL;DR: This review collected about 100 circRNA-associated bioinformatics tools and summarized their current attributes and capabilities and performed network analysis and text mining on circRNA tool publications in order to reveal trends in their ongoing development.
Journal ArticleDOI
Silencing CDR1as inhibits colorectal cancer progression through regulating microRNA-7.
Wentao Tang,Meiling Ji,Guodong He,Liangliang Yang,Zhengchuan Niu,Mi Jian,Ye Wei,Li Ren,Jianmin Xu +8 more
TL;DR: Downregulation of CDR1as suppressed CRC cell proliferation and invasion and increased microRNA-7 (miR-7) expression, and Mechanistic studies demonstrated that CDR 1as silencing suppressed EGFR and IGF-1R expression, which could be partially blocked by the miR- 7 inhibitor.
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