Slicing and dicing viruses: antiviral
            <scp>RNA</scp>
            interference in mammals

Maillard, Pierre V; Veen, Annemarthe G. van der; Poirier, Enzo Z.; Sousa, Caetano Reis e

doi:10.15252/embj.2018100941

Cited by 111 publications

(112 citation statements)

References 189 publications

(218 reference statements)

Supporting

Mentioning

106

Contrasting

Unclassified

Order By: Relevance

“…Having established that HCV NS2 contains RNAi suppression activity, we sought to examine the detailed mechanism through which HCV NS2 inhibits RNAi. In the process of RNAi, dsRNA/shRNA requires the Dicer-mediated cleavage into siRNA (Maillard et al 2019). To investigate whether HCV NS2 can inhibit this step, small RNAs harvested from HEK293T cells co-expressing EGFP-specific shRNA together with NS2 were subjected to Northern blotting with a DIG-labeled RNA probe targeting EGFP siRNA produced from shRNA by Dicer.…”

Section: Hcv Ns2 Protein Inhibits Dicer-mediated Sirna Generation By mentioning

confidence: 99%

“…S1B). Because the dsRNA/ siRNA-binding and protein dimerization are critical for VSR's activity (Maillard et al 2019), the positivelycharged and highly conserved residues, including arginine (R), lysine (K), histidine (H), glutamic acid (E) and cysteine (C) were subjected to single-point mutation to alanine (A), and the resulting mutant NS2 proteins were then examined via the reversal-of-silencing assay in HEK293T cells (Fig. 5A-5C).…”

Section: C184a Of Hcv Ns2 Is Critical For the Vsr Activitymentioning

confidence: 99%

“…RNAi is an evolutionarily conserved mechanism in all eukaryotes for post-transcriptional gene silencing. RNAi serves as an important antiviral immune response in a wide range of organisms, including fungi, plants, and invertebrates (Guo et al 2019;Maillard et al 2019). Moreover, recent studies have demonstrated that RNAi also exerts antiviral effects in mammals Maillard et al 2013;Li et al 2016;Qiu et al 2017;Xu et al 2019).…”

Section: Introductionmentioning

confidence: 99%

“…These vRI-dsRNAs can be recognized and cleaved by host endoribonuclease Dicer into virus-derived small interfering RNAs (vsiRNAs) of approximately 21-23 nucleotide (nt). Argonaute (AGO) protein within RNA-induced silencing complexes (RISCs) incorporates one of the strands of vsiRNA duplex, which directs the RISC-mediated degradation of cognate viral RNAs (Maillard et al 2019).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Hepatitis C Virus NS2 Protein Suppresses RNA Interference in Cells

Zhou

Shu

et al. 2019

Virol. Sin.

View full text Add to dashboard Cite

RNAi interference (RNAi) is an evolutionarily conserved post-transcriptional gene silencing mechanism and has been well recognized as an important antiviral immunity in eukaryotes. Numerous viruses have been shown to encode viral suppressors of RNAi (VSRs) to antagonize antiviral RNAi. Hepatitis C virus (HCV) is a medically important human pathogen that causes acute and chronic hepatitis. In this study, we screened all the nonstructural proteins of HCV and found that HCV NS2 could suppress RNAi induced either by small hairpin RNAs (shRNAs) or small interfering RNAs (siRNAs) in mammalian cells. Moreover, we demonstrated that NS2 could suppress RNAi via its direct interaction with doublestranded RNAs (dsRNAs) and siRNAs, and further identified that the cysteine 184 of NS2 is required for the RNAi suppression activity through a serial of point mutation analyses. Together, our findings uncovered that HCV NS2 can act as a VSR in vitro, thereby providing novel insights into the life cycle and virus-host interactions of HCV.Keywords Hepatitis C virus (HCV) Á NS2 Á Antiviral RNAi Á Viral suppressor of RNAi (VSR)

show abstract

Section: Hcv Ns2 Protein Inhibits Dicer-mediated Sirna Generation By mentioning

confidence: 99%

Section: C184a Of Hcv Ns2 Is Critical For the Vsr Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Hepatitis C Virus NS2 Protein Suppresses RNA Interference in Cells

Zhou

Shu

et al. 2019

Virol. Sin.

View full text Add to dashboard Cite

show abstract

“…These vsiRNAs are integrated into the Argonaute protein within the RNA-induced silencing complex (RISC) to degrade complementary viral RNAs in a sequence-specific manner [11]. Because vsiRNAs are derived from vi-dsRNAs, vsiRNAs serve as the specificity determinants of antiviral RNAi defence [12].…”

Section: Introductionmentioning

confidence: 99%

The 3A protein of coxsackievirus B3 acts as a viral suppressor of RNA interference

Zhang

et al. 2020

Journal of General Virology

View full text Add to dashboard Cite

RNA interference (RNAi) is a potent antiviral defence mechanism in eukaryotes, and numerous viruses have been found to encode viral suppressors of RNAi (VSRs). Coxsackievirus B3 (CVB3) belongs to the genus Enterovirus in the family Picornaviridae, and has been reported to be a major causative pathogen for viral myocarditis. Despite the importance of CVB3, it is unclear whether CVB3 can also encode proteins that suppress RNAi. Here, we showed that the CVB3 nonstructural protein 3A suppressed RNAi triggered by either small hairpin RNAs (shRNAs) or small interfering RNAs (siRNAs) in mammalian cells. We further uncovered that CVB3 3A interacted directly with double-stranded RNAs (dsRNAs) and siRNAs in vitro. Through mutational analysis, we found that the VSR activity of CVB3 3A was significantly reduced by mutations of D24A/L25A/L26A, Y37A/C38A and R60A in conserved residues. In addition, the 3A protein encoded by coxsackievirus B5 (CVB5), another member of Enterovirus, also showed VSR activity. Taken together, our findings showed that CVB3 3A has in vitro VSR activity, thereby providing insights into the pathogenesis of CVB3 and other enteroviruses.

show abstract

Small RNAs in epigenetic inheritance: from mechanisms to trait transmission

Cecere

2021

FEBS Letters

View full text Add to dashboard Cite

Inherited information is transmitted to progeny primarily by the genome through the gametes. However, in recent years, epigenetic inheritance has been demonstrated in several organisms, including animals. Although it is clear that certain post-translational histone modifications, DNA methylation, and noncoding RNAs regulate epigenetic inheritance, the molecular mechanisms responsible for epigenetic inheritance are incompletely understood. This review focuses on the role of small RNAs in transmitting epigenetic information across generations in animals. Examples of documented cases of transgenerational epigenetic inheritance are discussed, from the silencing of transgenes to the inheritance of complex traits, such as fertility, stress responses, infections, and behavior. Experimental evidence supporting the idea that small RNAs are epigenetic molecules capable of transmitting traits across generations is highlighted, focusing on the mechanisms by which small RNAs achieve such a function. Just as the role of small RNAs in epigenetic processes is redefining the concept of inheritance, so too our understanding of the molecular pathways and mechanisms that govern epigenetic inheritance in animals is radically changing.

show abstract

Slicing and dicing viruses: antiviral RNA interference in mammals

Cited by 111 publications

References 189 publications

Hepatitis C Virus NS2 Protein Suppresses RNA Interference in Cells

Hepatitis C Virus NS2 Protein Suppresses RNA Interference in Cells

The 3A protein of coxsackievirus B3 acts as a viral suppressor of RNA interference

Small RNAs in epigenetic inheritance: from mechanisms to trait transmission

Contact Info

Product

Resources

About