Detecting circular RNAs: bioinformatic and experimental challenges
Linda Szabo,Julia Salzman +1 more
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TL;DR: This work reviews sources of experimental and bioinformatic biases that complicate the accurate discovery of circRNAs and discusses statistical approaches to address these biases.
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Abstract: The pervasive expression of circular RNAs (circRNAs) is a recently discovered feature of gene expression in highly diverged eukaryotes. Numerous algorithms that are used to detect genome-wide circRNA expression from RNA sequencing (RNA-seq) data have been developed in the past few years, but there is little overlap in their predictions and no clear gold-standard method to assess the accuracy of these algorithms. We review sources of experimental and bioinformatic biases that complicate the accurate discovery of circRNAs and discuss statistical approaches to address these biases. We conclude with a discussion of the current experimental progress on the topic.
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Citations
Identification of plasma hsa_circ_0008673 expression as a potential biomarker and tumor regulator of breast cancer
TL;DR: This study aimed to investigate plasma cell‐free circRNAs as a novel class of biomarkers for the diagnosis of breast cancer.
The emerging role of circular RNAs in breast cancer.
Siying Zhou,Wei Chen,Sujin Yang,Zi-han Xu,Jia-Hua Hu,He-da Zhang,Shanliang Zhong,Jinhai Tang,Jinhai Tang +8 more
TL;DR: Biogenesis and function of circRNAs are concentrated on, their implications in BCa are summarized, and their potential as diagnostic and therapeutic targets for BCa is discussed.
Circular RNAs in Cardiovascular Physiopathology: From Molecular Mechanisms to Therapeutic Opportunities
Giorgia Capirossi,Sofia Brasini,Elena Tremoli,Andrea Binatti,Roberta Roncarati,Giorgia Capirossi,Sofia Brasini,Elena Tremoli,Andrea Binatti,Roberta Roncarati +9 more
Abstract: Circular RNAs are a class of stable non-coding RNAs generated through a back-splicing mechanism. They are now recognized as central players in cell function and are no longer considered byproducts of transcription. CircRNAs regulate gene expression at the transcriptional, post-transcriptional, and translational levels by interacting with various molecules. They act as sponges for miRNAs and proteins, molecular scaffolds, and can also be translated into peptides. Although advances in next-generation sequencing and PCR methods have improved their identification and quantification, technical and bioinformatic challenges remain. Increasing evidence shows their involvement in cardiovascular diseases such as heart failure, hypertrophy, fibrosis, and atherosclerosis, with protective or deleterious effects depending on the context. Given their presence in biological fluids and extracellular vesicles, they can be considered promising biomarkers, but their therapeutic applications are still under investigation. Future studies including a better understanding of their mechanisms of action, the development of standardized validation methods, and potential clinical applications (prevention, early diagnosis, personalized therapies) in diseases are still needed. This review provides an updated overview of the knowledge regarding circRNAs and their translational role in health and disease with a particular focus on cardiovascular diseases.
Biology of Circular RNAs and Methodological Approaches to Their Study
Michaela Ruckova,Dagmar Al Tukmachi,Ondřej Slabý +2 more
TL;DR: CircRNAs are highly stable non-coding RNAs that regulate gene expression and have potential for use as biomarkers and therapeutic targets. Their unique structure and function make them an active field of research with ongoing challenges in characterization and understanding their regulation.
Circular RNAs in prostate cancer: Biogenesis,biological functions, and clinical significance.
Xiao Liu,Yonghua Tong,Ding Xia,Ejun Peng,Xiaoqi Yang,Hailang Liu,Tao Ye,Xinguang Wang,Yu He,Zhangqun Ye,Zhiqiang Chen,Kun Tang +11 more
TL;DR: In this article, the current research status of circRNAs in prostate cancer is briefly reviewed, and the potential therapeutic targets are discussed, considering their critical regulatory roles in the progression of prostate cancer.
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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.
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.
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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.
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.
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