Mutual Regulation of RNA Silencing and the IFN Response as an Antiviral Defense System in Mammalian Cells

Takahashi, Tomoko; Ui-Tei, Kumiko

doi:10.3390/ijms21041348

Cited by 16 publications

(12 citation statements)

References 111 publications

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“…These observations could be due to the fact that several mammalian viruses potentially encode VSR proteins, thereby masking the effect of RNAi [ 22 , 28 , 29 , 52 , 57 ]. Another putative but non-exclusive explanation could be that there is a mutual regulation of type I IFN and RNAi pathways [ 58 , 59 ]. Thus, it has already been shown that PACT can regulate MDA5 and RIG-I during virus infection and therefore the induction of type I IFN response [ 60 , 61 ].…”

Section: Discussionmentioning

confidence: 99%

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Human DICER helicase domain recruits PKR and modulates its antiviral activity

et al. 2021

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The antiviral innate immune response mainly involves type I interferon (IFN) in mammalian cells. The contribution of the RNA silencing machinery remains to be established, but several recent studies indicate that the ribonuclease DICER can generate viral siRNAs in specific conditions. It has also been proposed that type I IFN and RNA silencing could be mutually exclusive antiviral responses. In order to decipher the implication of DICER during infection of human cells with alphaviruses such as the Sindbis virus and Semliki forest virus, we determined its interactome by proteomics analysis. We show that DICER specifically interacts with several double-stranded RNA binding proteins and RNA helicases during viral infection. In particular, proteins such as DHX9, ADAR-1 and the protein kinase RNA-activated (PKR) are enriched with DICER in virus-infected cells. We demonstrate that the helicase domain of DICER is essential for this interaction and that its deletion confers antiviral properties to this protein in an RNAi-independent, PKR-dependent, manner.

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Section: Discussionmentioning

confidence: 99%

“…mutual regulation of type I IFN and RNAi pathways [58,59]. Thus, it has already been shown that PACT can regulate MDA5 and RIG-I during virus infection and therefore the induction of type I IFN response [60,61].…”

Section: Plos Pathogensmentioning

confidence: 99%

Human DICER helicase domain recruits PKR and modulates its antiviral activity

et al. 2021

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“…These observations could be due to the fact that several mammalian viruses potentially encode VSR proteins, thereby masking the effect of RNAi (Li et al, 2013(Li et al, , 2016Maillard et al, 2013;Qiu et al, 2017Qiu et al, , 2020. Another putative but non-exclusive explanation could be that there is a mutual regulation of type I IFN and RNAi pathways (Berkhout, 2018;Takahashi and Ui-Tei, 2020). Thus, it has already been shown that PACT can regulate MDA5 and RIG-I during virus infection and therefore the induction of type I IFN response (Kok et al, 2011;Lui et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Human DICER helicase domain recruits PKR and modulates its antiviral activity

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et al. 2020

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20The innate immune response against viruses mainly involves type I interferon (IFN) in 21 mammalian cells. The exact contribution of the RNA silencing machinery remains to be 22 established, but several recent studies indicate that the type III ribonuclease DICER can 23 generate viral siRNAs in specific conditions. In addition, it has been proposed that type I IFN 24and RNA silencing could be mutually exclusive antiviral responses. In order to decipher the 25 implication of DICER during infection of human cells with the Sindbis virus, we determined 26 its interactome by immunoprecipitation and mass spectrometry analysis. Our results show that 27 human DICER specifically interacts with several double-stranded RNA binding proteins and 28 RNA helicases during viral infection. In particular, proteins such as DHX9, ADAR-1 and the 29 protein kinase RNA-activated (PKR) are enriched with DICER in virus-infected cells. We 30 demonstrated the importance of DICER helicase domain in its interaction with PKR and 31showed that it has functional consequences for the cellular response to viral infection. 32 33 dsRNA or miRNA precursor, DICER relies on interacting with co-factors to be fully functional. 59

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“…Transfection of murine ESCs with EMCV produced intracellular EMCV-derived siRNAs with a certain size and 3’ overhangs nucleotides [ 66 , 95 ]. It seems that the simultaneous degradation of RNAi and the promotion of IFN-related responses could overlap once anti-viral immunity is initiated [ 154 , 155 ]. The suppression of MAVS in mouse embryonic fibroblasts aborted the functionality and collaboration of dsRNA sensors with IFN products [ 96 ].…”

Section: Antiviral Mechanisms Of Stem Cellsmentioning

confidence: 99%