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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Role of circular RNAs in brain development and CNS diseases.
TL;DR: A better understanding of the circRNA function will help to develop novel therapeutic strategies to treat CNS complications and the involvement of various circRNAs in brain development and CNS diseases is discussed.
Journal ArticleDOI
Circular BANP, an upregulated circular RNA that modulates cell proliferation in colorectal cancer.
TL;DR: It is demonstrated that dysregulated circ-BANP appears to have an important role in CRC cells and could serve as a prognostic and therapeutic marker for CRC.
Journal ArticleDOI
Functional role of circular RNAs in cancer development and progression.
TL;DR: A detailed description of biological functions, molecular role of circRNAs in different cancers, and its potential role as biomarkers in a clinical context is provided.
Journal ArticleDOI
Altered expression pattern of circular RNAs in primary and metastatic sites of epithelial ovarian carcinoma
Ikhlak Ahmed,Thasni Karedath,Simeon S. Andrews,Iman K. Al-Azwani,Yasmin A. Mohamoud,Denis Querleu,Arash Rafii,Joel A. Malek +7 more
TL;DR: An in-house computational pipeline was developed to identify and characterize the circRNA expression from paired-end RNA-Seq libraries and revealed thousands of circular isoforms in Epithelial Ovarian Carcinoma, indicating their suitability as biomarkers in highly heterogeneous cancer transcriptomes.
Journal ArticleDOI
CircRNA hsa_circRNA_101996 increases cervical cancer proliferation and invasion through activating TPX2 expression by restraining miR-8075.
TL;DR: A novel mechanism that hsa_circRNA_101996‐miR‐8075‐TPX2 network promoted cervical cancer progression was revealed, which was related to poor outcomes of cervical cancer patients.
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