Circular RNAs: Biogenesis, Function and Role in Human Diseases.
John Greene,John Greene,Anne-Marie Baird,Lauren Brady,Marvin Lim,Steven G. Gray,Raymond S. McDermott,Stephen P. Finn +7 more
TLDR
It has been proposed that circRNA regulate gene expression at the transcriptional or post-transcriptional level by interacting with miRNAs and that circRNAs may have a role in regulating miRNA function in cancer initiation and progression.Abstract:
Circular RNAs (circRNAs) are currently classed as non-coding RNA (ncRNA) that, unlike linear RNAs, form covalently closed continuous loops and act as gene regulators in mammals. They were originally thought to represent errors in splicing and considered to be of low abundance, however, there is now an increased appreciation of their important function in gene regulation. circRNAs are differentially generated by backsplicing of exons or from lariat introns. Unlike linear RNA, the 3′ and 5′ ends normally present in an RNA molecule have been joined together by covalent bonds leading to circularisation. Interestingly, they have been found to be abundant, evolutionally conserved and relatively stable in the cytoplasm. These features confer numerous potential functions to circRNAs, such as acting as miRNA sponges, or binding to RNA-associated proteins to form RNA-protein complexes that regulate gene transcription. It has been proposed that circRNA regulate gene expression at the transcriptional or post-transcriptional level by interacting with miRNAs and that circRNAs may have a role in regulating miRNA function in cancer initiation and progression. circRNAs appear to be more often downregulated in tumour tissue compared to normal tissue and this may be due to (i) errors in the back-splice machinery in malignant tissues, (ii) degradation of circRNAs by deregulated miRNAs in tumour tissue or (iii) increasing cell proliferation leading to a reduction of circRNAs. circRNAs have been identified in exosomes and more recently, chromosomal translocations in cancer have been shown to generate aberrant fusion-circRNAs associated with resistance to drug treatments. In addition, though originally thought to be non-coding, there is now increasing evidence to suggest that select circRNAs can be translated into functional proteins. Although much remains to be elucidated about circRNA biology and mechanisms of gene regulation, these ncRNAs are quickly emerging as potential disease biomarkers and therapeutic targets in cancer.read more
Citations
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Circbank: a comprehensive database for circRNA with standard nomenclature.
TL;DR: circbank is presented, a comprehensive database for human circRNAs, where a novel naming system based on the host genes ofcircRNAs was implemented, and other five features of circ RNAs including the miRNA binding site, conservation of circRN as, m6A modification ofcirc RNAs, mutation of Circbank, and protein-coding potential of circRNA are collected.
Journal ArticleDOI
Molecular roles and function of circular RNAs in eukaryotic cells.
TL;DR: It is described how circRNAs impact gene expression of their host gene locus by affecting transcriptional initiation and elongation or splicing, and how they partake in controlling the function of other molecules, for example by interacting with microRNAs and proteins.
Journal ArticleDOI
Three isoforms of exosomal circPTGR1 promote hepatocellular carcinoma metastasis via the miR449a–MET pathway
Guoying Wang,Wei Liu,Yong Zou,Gen-shu Wang,Yinan Deng,Jingyan Luo,Yingcai Zhang,Hua Li,Qi Zhang,Yang Yang,Guihua Chen +10 more
TL;DR: Higher metastatic HCC cells can confer this potential on those with lower or no metastatic potential via exosomes with circPTGR1, resulting in increased migratory and invasive abilities in those cells.
Journal ArticleDOI
Circular RNA hsa_circ_0003575 regulates oxLDL induced vascular endothelial cells proliferation and angiogenesis
Chen-Ye Li,Lan Ma,Bo Yu +2 more
TL;DR: Human circRNA microarray analysis reveals the expression profiles of HUVECs and verifies the role of hsa_circ_0003575 on HUV ECs, providing a therapeutic strategy for vascular endothelial cell injury of atherosclerosis.
Journal ArticleDOI
Circular RNAs: a new frontier for cancer diagnosis and therapy.
Miaoci Zhang,Yan Xin +1 more
TL;DR: Understanding of circRNAs helps to add a new dimension to the molecular structure of cancer and will provide many new opportunities for cancer treatment.
References
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Journal ArticleDOI
Circular RNAs are a large class of animal RNAs with regulatory potency
Sebastian Memczak,Marvin Jens,Antigoni Elefsinioti,Francesca Torti,Janna Krueger,Agnieszka Rybak,Luisa Maier,Sebastian D. Mackowiak,Lea H. Gregersen,Mathias Munschauer,Alexander Loewer,Ulrike Ziebold,Markus Landthaler,Christine Kocks,Ferdinand le Noble,Nikolaus Rajewsky +15 more
TL;DR: It is found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7.
Journal ArticleDOI
Natural RNA circles function as efficient microRNA sponges
Thomas B. Hansen,Trine I. Jensen,Bettina Hjelm Clausen,Jesper B. Bramsen,Bente Finsen,Christian Kroun Damgaard,Jørgen Kjems +6 more
TL;DR: This study serves as the first functional analysis of a naturally expressed circular RNA, ciRS-7, which contains more than 70 selectively conserved miRNA target sites, and is highly and widely associated with Argonaute proteins in a miR-7-dependent manner.
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.
Journal ArticleDOI
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
TL;DR: 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.
Journal ArticleDOI
circRNA Biogenesis Competes with Pre-mRNA Splicing
Reut Ashwal-Fluss,Markus Meyer,Nagarjuna Reddy Pamudurti,Andranik Ivanov,Osnat Bartok,Mor Hanan,Naveh Evantal,Sebastian Memczak,Nikolaus Rajewsky,Sebastian Kadener +9 more
TL;DR: Evidence that animal circRNAs are generated cotranscriptionally and that their production rate is mainly determined by intronic sequences is provided and it is demonstrated that circularization and splicing compete against each other.