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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Circular RNA: new star, new hope in cancer.
TL;DR: Recent advances on circularRNAs in cancer are summerized and a circular RNA network associated with tumorigenesis is described, suggesting that circular RNAs can serve as newly developed biomarkers with clinic implications.
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A large-scale circular RNA profiling reveals universal molecular mechanisms responsive to drought stress in maize and Arabidopsis.
TL;DR: A large-scale circRNA profiling identified 2174 and 1354 high-confidence circRNAs in maize and Arabidopsis, respectively, and most were differentially expressed in response to drought, suggesting important roles in maize drought responses or their potential use as biomarkers for breeding drought-tolerant maize.
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Non-coding RNAs turn up the heat: an emerging layer of novel regulators in the mammalian heat shock response.
Robert F. Place,Emily J. Noonan +1 more
TL;DR: An updated model integrating the traditional heat shock response with the activities of regulatory ncRNA is presented, which expands on the mechanisms for efficient execution of the stress response, while offering a more comprehensive summary of the major regulators and responders in heat shock signaling.
Journal ArticleDOI
Circular RNA hsa_circ_0000523 regulates the proliferation and apoptosis of colorectal cancer cells as miRNA sponge
TL;DR: It was demonstrated that the expression of circRNA hsa_circ_0000523 (also known as circ_006229) was down-regulated in different colorectal cancer cell lines and it was found that miR-31 could recognize hsa-circ-0000523 sequence and that it acted as a “sponge” of mi-31, indirectly regulating Wnt/β-catenin signaling pathway, which was involved in the progression of coloreCTal cancer
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Comprehensive CircRNA expression profile and selection of key CircRNAs during priming phase of rat liver regeneration
TL;DR: This paper is the first to employ the comprehensive circRNA expression profile and to investigate circRNA-miRNA interactions during priming phase of rat LR, laying the foundation for revealing the functional roles of circRNAs during rat LR and help solve the remaining clinical problems.
References
More filters
Journal ArticleDOI
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
TL;DR: A new method of total RNA isolation by a single extraction with an acid guanidinium thiocyanate-phenol-chloroform mixture is described, providing a pure preparation of undegraded RNA in high yield and can be completed within 4 h.
Journal ArticleDOI
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.
TL;DR: By following this protocol, investigators are able to gain an in-depth understanding of the biological themes in lists of genes that are enriched in genome-scale studies.
Journal ArticleDOI
BEDTools: a flexible suite of utilities for comparing genomic features
Aaron R. Quinlan,Ira M. Hall +1 more
TL;DR: A new software suite for the comparison, manipulation and annotation of genomic features in Browser Extensible Data (BED) and General Feature Format (GFF) format, which allows the user to compare large datasets (e.g. next-generation sequencing data) with both public and custom genome annotation tracks.
Journal ArticleDOI
Integrative genomics viewer
James T. Robinson,Helga Thorvaldsdottir,Wendy Winckler,Mitchell Guttman,Eric S. Lander,Eric S. Lander,Gad Getz,Jill P. Mesirov +7 more
TL;DR: In this article, the authors present an approach for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data.
Journal ArticleDOI
Non-coding RNAs in human disease
TL;DR: Dysregulation of these ncRNAs is being found to have relevance not only to tumorigenesis, but also to neurological, cardiovascular, developmental and other diseases, and there is great interest in therapeutic strategies to counteract these perturbations.