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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Identification of differentially expressed circular RNAs in human colorectal cancer.
Peili Zhang,Zhigui Zuo,Wenjing Shang,Aihua Wu,Ruichun Bi,Jianbo Wu,Shaotang Li,Xuecheng Sun,Lei Jiang +8 more
TL;DR: It is suggested that hsa_circRNA_103809 and hsa-circ RNA_104700 may be potentially involved in the development of colorectal cancer and serve as potential biomarkers for the diagnosis of coloresceptic cancer.
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Dynamic Alu Methylation during Normal Development, Aging, and Tumorigenesis
TL;DR: This review focuses on the dynamic Alu methylation during development, aging, and tumor genesis and the cause and consequence of AlU methylation changes will be discussed.
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Circular RNA of cattle casein genes are highly expressed in bovine mammary gland
TL;DR: The deep RNA-sequencing technique known as RNA-seq was used to compare expression profiles of circRNAs from 2 pooled RNA samples from cow mammary gland on d 90 and 250 postpartum and to identify the key circ RNAs involved in lactation.
Journal ArticleDOI
Circular RNAs as Promising Biomarkers: A Mini-Review.
Nadiah Abu,A. Rahman A. Jamal +1 more
TL;DR: This mini-review attempts to concisely look at the biology of circularRNAs, the putative functional activities, the prevalence of circular RNAs, and the possible role of circular RNA as biomarkers for diagnosis or measuring drug response.
Journal ArticleDOI
Identification of circRNA–miRNA–mRNA regulatory network in gastric cancer by analysis of microarray data
TL;DR: A deeper understanding is provided of the circRNA-related competing endogenous RNA regulatory mechanism in GC pathogenesis to provide a deeper understanding of tumorigenesis and cancer progression.
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.