Circular Nucleic Acids: Discovery, Functions and Applications

Li, Jiuxing; Mohammed-Elsabagh, Mostafa; Paczkowski, Freeman; Li, Yingfu

doi:10.1002/cbic.202000003

Cited by 46 publications

(36 citation statements)

References 298 publications

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“…The ring structures add to the weight of evidence that the oligomers synthesized by wetdry cycles resemble RNA in their physical properties 23,24 , and similar ring structures has 210 been observed with DNA 25 . Furthermore, the sizes of the rings are well beyond the minimum range required for catalytic or genetic structures to form.…”

supporting

confidence: 71%

Viroid-sized rings self-assemble from mononucleotides through wet-dry cycling: implications for the origin of life

Hassenkam

Damer

Mednick

et al. 2020

Preprint

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It is possible that early life relied on RNA polymers that served as ribozyme-like catalysts and store genetic information 1,2 . The source of such polymers is uncertain, but previous investigations reported that wet-dry cycles simulating prebiotic hot 20 springs provide sufficient energy to drive condensation reactions of mononucleotides to form oligomers 3 . The aim of the study reported here was to visualize the products by atomic force microscopy. In addition to globular oligomers, ring-like structures ranging from 10-200 nm in diameter with an average around 30-40 nm were abundant, particularly when nucleotides capable of base pairing were present. The 25 thickness of the rings was consistent with single stranded products, but some had thicknesses indicating base pair stacking. Others had more complex structures in the form of short polymer attachments and pairing of rings. These observations suggest the possibility that template-directed synthesis may occur during wet-dry cycling followed by solvation of the rings. We conclude that RNA-like rings and structures 30 could have been synthesized non-enzymatically on the prebiotic Earth with sizes sufficient to fold into ribozymes and genetic molecules required for life to begin.

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supporting

confidence: 71%

Viroid-sized rings self-assemble from mononucleotides through wet-dry cycling: implications for the origin of life

Hassenkam

Damer

Mednick

et al. 2020

Preprint

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show abstract

“…The approach was to develop a closed circular RNA coding for miRNAs. A circular RNA is not readily degraded by exonucleases and the inherent higher stability of dsRNAs compared with ssRNAs may contribute to an increased half-life (34). Increased stability of db34a compared with linear RNA was observed in the present study.…”

Section: Discussionsupporting

confidence: 44%

Circular dumbbell miR‑34a‑3p and ‑5p suppresses pancreatic tumor cell‑induced angiogenesis and activates macrophages

Gnanamony

Demirkhanyan

et al. 2020

Oncol Lett

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Angiogenesis is a tightly regulated biological process by which new blood vessels are formed from pre-existing blood vessels. This process is also critical in diseases such as cancer. Therefore, angiogenesis has been explored as a drug target for cancer therapy. The future of effective anti-angiogenic therapy lies in the intelligent combination of multiple targeting agents with novel modes of delivery to maximize therapeutic effects. Therefore, a novel approach is proposed that utilizes dumbbell RNA (dbRNA) to target pathological angiogenesis by simultaneously targeting multiple molecules and processes that contribute to angiogenesis. In the present study, a plasmid expressing miR-34a-3p and-5p dbRNA (db34a) was constructed using the permuted intron-exon method. A simple protocol to purify dbRNA from bacterial culture with high purity was also developed by modification of the RNASwift method. To test the efficacy of db34a, pancreatic cancer cell lines PANC-1 and MIA PaCa-2 were used. Functional validation of the effect of db34a on angiogenesis was performed on human umbilical vein endothelial cells using a tube formation assay, in which cells transfected with db34a exhibited a significant reduction in tube formation compared with cells transfected with scrambled dbRNA. These results were further validated in vivo using a zebrafish angiogenesis model. In conclusion, the present study demonstrates an approach for blocking angiogenesis using db34a. The data also show that this approach may be used to targeting multiple molecules and pathways.

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“…Sanger et al (13) first identified the structural characteristics of circRNA, which comprise a single-stranded, highly stable and closed loop structure lacking a 5'cap or 3'poly-A tail. Numerous circRNA molecules have been identified in eukaryotic cells and tissues and were found to be constructed from selective exonic and intronic repeats that base-pair to one another (14). The involvement of back-splicing and exon-skipping in circRNA formation have been confirmed in vitro and in vivo (15).…”

Section: Biogenesis and Function Of Circrnamentioning

confidence: 98%

Underlying metastasis mechanism and clinical application of exosomal circular RNA in tumors (Review)

et al. 2021

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Circular RNA (circRNA) is a long non-coding RNA molecule with a closed loop structure lacking a 5'cap and 3'tail. circRNA is stable, difficult to cleave and resistant to RNA exonuclease or RNase R degradation. circRNA molecules have several clinical applications, especially in tumors. For instance, circRNA may be used for non-invasive diagnosis, therapy and prognosis. Exosomes play a crucial role in the development of tumors. Exosomal circRNA in particular has led to increased research interest into tumorigenesis and tumor progression. Additionally, exosomal circRNA plays a role in cell-cell communication. Exosomal circRNA facilitates tumor metastasis by altering the tumor microenvironment and the pre-metastatic niche. Additionally, studies have revealed the mechanism by which exosomal circRNA affects malignant progression through signal transduction. Moreover, exosomal circRNA promotes tumor metastasis by regulating gene expression, RNA transcription and protein translation. In this review, the biological features and clinical application of exosomal circRNA are described, highlighting the underlying mechanisms through which they regulate tumor metastasis. The application of circRNA as clinical diagnostic biomarkers and in the development of novel therapeutic strategies is also discussed.

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Circular Nucleic Acids: Discovery, Functions and Applications

Cited by 46 publications

References 298 publications

Viroid-sized rings self-assemble from mononucleotides through wet-dry cycling: implications for the origin of life

Viroid-sized rings self-assemble from mononucleotides through wet-dry cycling: implications for the origin of life

Circular dumbbell miR‑34a‑3p and ‑5p suppresses pancreatic tumor cell‑induced angiogenesis and activates macrophages

Underlying metastasis mechanism and clinical application of exosomal circular RNA in tumors (Review)

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