Circle the Wagons: Circular RNAs Control Innate Immunity

Wilusz, Jeremy E.

doi:10.1016/j.cell.2019.04.020

Cited by 16 publications

(10 citation statements)

References 10 publications

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“…The immune response in human beings undergoes a "butterfly effect", initiated from intracellular innate immune sensing to a global adaptive immune response 29 . Virus-encoded molecular signatures, such as cytosolic dsRNA or otherwise foreign "nonself" RNA species, trigger cellular antiviral innate immune signaling, which is beneficial for the maintenance of body homeostasis during infections [29][30][31][32] . It is widely accepted that cytosolic RNA sensors RLRs, RIG-I, and MDA5 recognize these "non-self" RNAs and activate signal transduction pathways to induce a status of antiviral defense with expression of type I IFNs 27 .…”

Section: Discussionmentioning

confidence: 99%

N6-methyladenosine RNA modification suppresses antiviral innate sensing pathways via reshaping double-stranded RNA

Qiu

Zhang²,

Zhang

et al. 2021

Nat Commun

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Double-stranded RNA (dsRNA) is a virus-encoded signature capable of triggering intracellular Rig-like receptors (RLR) to activate antiviral signaling, but whether intercellular dsRNA structural reshaping mediated by the N6-methyladenosine (m6A) modification modulates this process remains largely unknown. Here, we show that, in response to infection by the RNA virus Vesicular Stomatitis Virus (VSV), the m6A methyltransferase METTL3 translocates into the cytoplasm to increase m6A modification on virus-derived transcripts and decrease viral dsRNA formation, thereby reducing virus-sensing efficacy by RLRs such as RIG-I and MDA5 and dampening antiviral immune signaling. Meanwhile, the genetic ablation of METTL3 in monocyte or hepatocyte causes enhanced type I IFN expression and accelerates VSV clearance. Our findings thus implicate METTL3-mediated m6A RNA modification on viral RNAs as a negative regulator for innate sensing pathways of dsRNA, and also hint METTL3 as a potential therapeutic target for the modulation of anti-viral immunity.

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Section: Discussionmentioning

confidence: 99%

N6-methyladenosine RNA modification suppresses antiviral innate sensing pathways via reshaping double-stranded RNA

Qiu

Zhang²,

Zhang

et al. 2021

Nat Commun

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“…CircRNAs are non-coding RNAs widely expressed in eukaryotic cells, and different from the traditional linear RNAs because of they are circular molecules (Kristensen et al, 2019 ; Liu C. et al, 2019 ; Vo et al, 2019 ; Wilusz, 2019 ; Zlotorynski, 2019 ). The characteristics of circRNA are high abundance, structure stable and highly tissue-specific expression.…”

Section: The Role Of Circrnas In Vmcmentioning

confidence: 99%

The Role of Non-coding RNAs in Viral Myocarditis

Zhang

Xiong

Zeng

et al. 2020

Front. Cell. Infect. Microbiol.

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Viral myocarditis (VMC) is a disease characterized as myocardial parenchyma or interstitium inflammation caused by virus infection, especially Coxsackievirus B3 (CVB3) infection, which has no accurate non-invasive examination for diagnosis and specific drugs for treatment. The mechanism of CVB3-induced VMC may be related to direct myocardial damage of virus infection and extensive damage of abnormal immune response after infection. Non-coding RNA (ncRNA) refers to RNA that is not translated into protein and plays a vital role in many biological processes. There is expanding evidence to reveal that ncRNAs regulate the occurrence and development of VMC, which may provide new treatment or diagnosis targets. In this review, we mainly demonstrate an overview of the potential role of ncRNAs in the pathogenesis, diagnosis and treatment of CVB3-induced VMC.

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“…In addition, in some studies, only a small sample size was collected to identify and quantify circRNAs, accompanied by the relatively low abundance of circRNAs, making it possible to acquire the false negatives or inexact expression profiles. Secondly, most of the current researches are still focusing on the exploration of targets and preliminary mechanism verification, but still lacking further mechanism exploration, such as the impact on tumor biogenesis, tumor immunology, and metabolic immune characteristics (Wilusz, 2019 ). Therefore, more supplementary studies are needed to investigate the molecular mechanisms of their biological functions in BC.…”

Section: Discussionmentioning

confidence: 99%

Circular RNAs: Their Role in the Pathogenesis and Orchestration of Breast Cancer

Xiao

Tan

et al. 2021

Front. Cell Dev. Biol.

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As one of the most frequently occurring malignancies in women, breast cancer (BC) is still an enormous threat to women all over the world. The high mortality rates in BC patients are associated with BC recurrence, metastatic progression to distant organs, and therapeutic resistance. Circular RNAs (circRNAs), belonging to the non-coding RNAs (ncRNAs), are connected end to end to form covalently closed single-chain circular molecules. CircRNAs are widely found in different species and a variety of human cells, with the features of diversity, evolutionary conservation, stability, and specificity. CircRNAs are emerging important participators in multiple diseases, including cardiovascular disease, inflammation, and cancer. Recent studies have shown that circRNAs are involved in BC progress by regulating gene expression at the transcriptional or post-transcriptional level via binding to miRNAs then inhibiting their function, suggesting that circRNAs may be potential targets for early diagnosis, treatment, and prognosis of BC. Herein, in this article, we have reviewed and summarized the current studies about the biogenesis, features, and functions of circRNAs. More importantly, we emphatically elucidate the pivotal functions and mechanisms of circRNAs in BC growth, metastasis, diagnosis, and drug resistance. Deciphering the complex networks, especially the circRNA-miRNA target gene axis, will endow huge potentials in developing therapeutic strategies for combating BC.

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Circle the Wagons: Circular RNAs Control Innate Immunity

Cited by 16 publications

References 10 publications

N6-methyladenosine RNA modification suppresses antiviral innate sensing pathways via reshaping double-stranded RNA

N6-methyladenosine RNA modification suppresses antiviral innate sensing pathways via reshaping double-stranded RNA

The Role of Non-coding RNAs in Viral Myocarditis

Circular RNAs: Their Role in the Pathogenesis and Orchestration of Breast Cancer

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