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
Reads0
Chats0
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
Citations
More filters
Journal ArticleDOI
Exosome-transported circRNA_0001236 enhances chondrogenesis and suppress cartilage degradation via the miR-3677-3p/Sox9 axis.
Guping Mao,Yiyang Xu,Yiyang Xu,Dianbo Long,Hong Sun,Hongyi Li,Ruobin Xin,Ziji Zhang,Li Zhiwen,Zhi Yang,Yan Kang +10 more
TL;DR: In this paper, the authors investigated whether exosomal circRNAs could act as competing endogenous RNAs (ceRNAs) to regulate the pathological process of osteoarthritis (OA).
Journal ArticleDOI
Identification and characterization of circular RNA in lactating mammary glands from two breeds of sheep with different milk production profiles using RNA-Seq.
Zhiyun Hao,Huitong Zhou,Jon G.H. Hickford,Hua Gong,Jiqing Wang,Jiang Hu,Xiu Liu,Shaobin Li,Mengli Zhao,Yuzhu Luo +9 more
TL;DR: An overview of circRNA expression in the ovine MG and the interaction between some key circRNAs and their target miRNAs is provided, which improves the knowledge of the role of circ RNA in sheep milk synthesis.
Journal ArticleDOI
Estrogen-induced circRNA, circPGR, functions as a ceRNA to promote estrogen receptor-positive breast cancer cell growth by regulating cell cycle-related genes.
Lei Wang,Jia Yi,Ling-yun Lu,Yue-ying Zhang,Lan Wang,Guo-sheng Hu,Yi-chen Liu,Jiancheng Ding,Hai-feng Shen,Fangqing Zhao,Hai-hua Huang,Wen Liu +11 more
TL;DR: Findings reveled that, besides the well-known messenger RNA (mRNA), microRNA (miRNA), long non-coding RNA (lncRNA) and enhancer RNA (eRNA) programs, estrogen also induced a circRNA program, and exemplified by circPGR, these estrogen-induced circRNAs were required for ER-positive breast cancer cell growth, providing a new class of therapeutic targets for ER, positive breast cancer.
Journal ArticleDOI
Circular RNAs: characteristics, biogenesis, mechanisms and functions in liver cancer.
TL;DR: In this article, the authors systematically evaluated the characteristics, biogenesis, mechanisms and functions of circRNAs in hepatocellular carcinoma (HCC) and further discussed the current shortcomings and potential directions of prospective studies on liver cancer-related circRNA.
Journal ArticleDOI
OUP accepted manuscript
TL;DR: In this paper , the authors found that the off-target effects of RxCas13d, a commonly used Cas13 effector, can be as strong as the level of on-target RNA knockdown.
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.