Biogenesis and Functions of Circular RNAs Come into Focus

Xiao, Mei-Sheng; Ai, Yuxi; Wilusz, Jeremy E.

doi:10.1016/j.tcb.2019.12.004

Cited by 253 publications

(211 citation statements)

References 117 publications

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“…CircRNAs are the back-splicing products of precursor mRNA [67] and exhibit widespread and cell typespecific m 6 A methylation features. Despite sharing m 6 A writers (METTL3/ METTL14) and readers (YTHDF1/ YTHDF2) that interact with mRNAs, many m 6 A sites on circRNAs are different from those on mRNAs.…”

Section: Circular Rnasmentioning

confidence: 99%

Interaction between N6-methyladenosine (m6A) modification and noncoding RNAs in cancer

et al. 2020

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As a critical internal RNA modification in higher eukaryotes, N 6-methyladenosine (m 6 A) has become the hotspot of epigenetics research in recent years. Extensive studies on messenger RNAs have revealed that m 6 A affects RNA fate and cell functions in various bioprocesses, such as RNA splicing, export, translation, and stability, some of which seem to be directly or indirectly regulated by noncoding RNAs. Intriguingly, abundant noncoding RNAs such as microRNAs, long noncoding RNAs, circular RNAs, small nuclear RNAs, and ribosomal RNAs are also highly modified with m 6 A and require m 6 A modification for their biogenesis and functions. Here, we discuss the interaction between m 6 A modification and noncoding RNAs by focusing on the functional relevance of m 6 A in cancer progression, metastasis, drug resistance, and immune response. Furthermore, the investigation of m 6 A regulatory proteins and its inhibitors provides new opportunities for early diagnosis and effective treatment of cancer, especially in combination with immunotherapy.

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Section: Circular Rnasmentioning

confidence: 99%

Interaction between N6-methyladenosine (m6A) modification and noncoding RNAs in cancer

et al. 2020

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“…One of the main problems of circRNA KD is the off-target effect, since linear cognate mRNA or other unrelated transcripts might be silenced as well [68]. More details can be found in recent reviews focused on technical issues related to circRNA analysis [69][70][71]. CRISPR-Cas genome-engineering techniques, in particular the CRISPR-Cas13 system, have been successfully utilized to genetically abolish circRNA formation [72].…”

Section: In Vitro Strategies For Circrna Kd and Komentioning

confidence: 99%

The Secret Garden of Neuronal circRNAs

Gasparini

Licursi

Presutti

et al. 2020

Cells

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High-throughput transcriptomic profiling approaches have revealed that circular RNAs (circRNAs) are important transcriptional gene products, identified across a broad range of organisms throughout the eukaryotic tree of life. In the nervous system, they are particularly abundant, developmentally regulated, region-specific, and enriched in genes for neuronal proteins and synaptic factors. These features suggested that circRNAs are key components of an important layer of neuronal gene expression regulation, with known and anticipated functions. Here, we review major recognized aspects of circRNA biogenesis, metabolism and biological activities, examining potential new functions in the context of the nervous system.

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“…4 Recently, due to the development of technology in bioinformatics, circRNAs illuminate critical functions in regulating cell cycle, inflammation, cell proliferation, and metabolic process. 5 Moreover, accumulating evidence has revealed the involvement of circRNAs in the pathology of autoimmune diseases, 6 cancers, 7 cardiovascular diseases, 8,9 and neurological diseases. 10 However, only limited studies have been conducted for clarifying the role of circRNAs in psoriasis.…”

Section: Introductionmentioning

confidence: 99%

hsa_circ_0003738 Inhibits the Suppressive Function of Tregs by Targeting miR-562/IL-17A and miR-490-5p/IFN-γ Signaling Pathway

Yang

Zhang

Bai

et al. 2020

Molecular Therapy - Nucleic Acids

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Dysfunction in the suppressive function of regulatory T cells (Tregs) has been related to the pathogenesis of psoriasis. Accumulating evidence has demonstrated the importance of circular RNAs (circRNAs) in regulating various biological process, such as cell proliferation, apoptosis, etc. However, the role of circR-NAs in modulating the suppressive functions of psoriatic Tregs and the underlying mechanisms have not been investigated. Here, by using circRNA microarray analysis, we discovered four upregulated and four downregulated circRNAs in psoriatic Tregs. Quantitative real-time PCR further confirmed a significant increase of circ_0003738 in psoriatic Tregs. Importantly, knockdown of circ_0003738 by lentivirus in psoriatic Tregs could restore their suppressive functions via inhibiting the secretion of proinflammatory cytokines interleukin-17A (IL-17A) and interferon (IFN)-g. Moreover, we found that circ_0003738 could bind to miR-562 to release the inhibition of target gene IL-17RA (IL-17 receptor A), thus promoting IL-17A signaling in psoriatic Tregs. In parallel, circ_0003738 acted also as a sponge for miR-490-5p and relieved inhibition for the target gene IFNGR2, which promoted IFN-g signaling in psoriatic Tregs. Our study demonstrated that upregulated circ_0003738 decreased the suppressive function of psoriatic Tregs via the miR-562/IL17RA and miR-490-5p/IFNGR2 (IFN-g receptor 2) axis, which indicated the involvement of circRNAs in the pathogenesis of dysfunctional Tregs. These findings will provide new therapeutic targets for the treatment of psoriasis.

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Biogenesis and Functions of Circular RNAs Come into Focus

Cited by 253 publications

References 117 publications

Interaction between N6-methyladenosine (m6A) modification and noncoding RNAs in cancer

Interaction between N6-methyladenosine (m6A) modification and noncoding RNAs in cancer

The Secret Garden of Neuronal circRNAs

hsa_circ_0003738 Inhibits the Suppressive Function of Tregs by Targeting miR-562/IL-17A and miR-490-5p/IFN-γ Signaling Pathway

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