The Caenorhabditis elegans RDE-10/RDE-11 Complex Regulates RNAi by Promoting Secondary siRNA Amplification

Zhang, Chi; Montgomery, Taiowa A.; Fischer, Sylvia E. J.; Garcia, Susana M. D. A.; Riedel, Christian G.; Fahlgren, Noah; Sullivan, Christopher; Carrington, James C.; Ruvkun, Gary

doi:10.1016/j.cub.2012.04.011

Cited by 53 publications

(102 citation statements)

References 37 publications

(90 reference statements)

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“…rsd-2 is known to contribute to the accumulation of secondary, but not primary, endogenous siRNAs (34). To find out whether RSD-2 contributes to RDVI through a similar mechanism, we checked the accumulation of viRNAs in rsd-2 mutants (tm1429) using Northern blotting.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, testing the rde-4 dependence of C04F12.1 may allow us to address the question of whether different worm AGO proteins specifically function in mechanistically distinct RDVI pathways in C. elegans. rsd-2 is known to be required for the accumulation of secondary, but not primary, endogenous siRNAs (34). Currently, it remains unclear whether rsd-2 contributes to RDVI through a similar mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…A recent study suggested that RSD-2 contributes to the accumulation of secondary siRNAs in both exogenous and endogenous RNAi pathways (34). Since rsd-2 mutants displayed defects in transposon silencing under unfavorable conditions, it is believed that RSD-2 plays an important role in maintaining chromosome integrity (35).…”

mentioning

confidence: 99%

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Antiviral RNA Silencing Initiated in the Absence of RDE-4, a Double-Stranded RNA Binding Protein, in Caenorhabditis elegans

Guo

Zhang

Wang

et al. 2013

J Virol

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Small interfering RNAs (siRNAs) processed from double-stranded RNA (dsRNA) of virus origins mediate potent antiviral defense through a process referred to as RNA interference (RNAi) or RNA silencing in diverse organisms. In the simple invertebrate Caenorhabditis elegans, the RNAi process is initiated by a single Dicer, which partners with the dsRNA binding protein RDE-4 to process dsRNA into viral siRNAs (viRNAs). Notably, in C. elegans this RNA-directed viral immunity (RDVI) also requires a number of worm-specific genes for its full antiviral potential. One such gene is rsd-2 (RNAi spreading defective 2), which was implicated in RDVI in our previous studies. In the current study, we first established an antiviral role by showing that rsd-2 null mutants permitted higher levels of viral RNA accumulation, and that this enhanced viral susceptibility was reversed by ectopic expression of RSD-2. We then examined the relationship of rsd-2 with other known components of RNAi pathways and established that rsd-2 functions in a novel pathway that is independent of rde-4 but likely requires the RNA-dependent RNA polymerase RRF-1, suggesting a critical role for RSD-2 in secondary viRNA biogenesis, likely through coordinated action with RRF-1. Together, these results suggest that RDVI in the single-Dicer organism C. elegans depends on the collective actions of both RDE-4-dependent and RDE-4-independent mechanisms to produce RNAi-inducing viRNAs. Our study reveals, for the first time, a novel siRNA-producing mechanism in C. elegans that bypasses the need for a dsRNA-binding protein.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Antiviral RNA Silencing Initiated in the Absence of RDE-4, a Double-Stranded RNA Binding Protein, in Caenorhabditis elegans

Guo

Zhang

Wang

et al. 2013

J Virol

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“…DCL2 functions in the antiviral response (Fusaro et al, 2006;Curtin et al, 2008;Donaire et al, 2008;Urayama et al, 2010;Zhang et al, 2012;Ogwok et al, 2016) where it produces viral siRNAs without www.efsa.europa.eu/publications 196 EFSA Supporting publication 2017:EN-1246…”

Section: Dcl2mentioning

confidence: 99%

Literature review of baseline information to support the risk assessment of RNAi‐based GM plants

Pačes

Nič²,

Novotný³

et al. 2017

EFSA Supporting Publications

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This report is the outcome of an EFSA procurement aiming at investigating and summarising the state of knowledge on (I) the mode-of-action of dsRNA and miRNA pathways, (II) the potential for nontarget gene regulation by dsRNA-derived siRNAs or miRNAs, (III) the determination of siRNA pools in plant tissues and the importance of individual siRNAs for silencing. The report is based on a comprehensive and systematic literature search, starting with the identification and retrieval of~190,000 publications related to the research area and further filtered down with keywords to produce focused collections used for subsequent screening of titles and abstracts. The report is comprised of an (I) Introduction to the field of small RNAs, (II) a Data and Methodologies section containing strategies used for literature search and study selection, and (III) the Results of the literature review organized according to the three main procurement tasks. The outcome of the first task reviews dsRNA and miRNA pathways in mammals (including humans), birds, fish, arthropods, annelids, molluscs, nematodes, and plants. Eight taxon-dedicated chapters are based on~1,400 cumulative references chosen from~10,000 inspected titles and abstracts. We review conserved and divergent aspects of small RNA pathways and dsRNA responses in animals and plants including structure and function of key proteins as well as four basic mechanisms: genome-encoded posttranscriptional regulations (miRNA), degradation of RNAs by short interfering RNA pools generated from long dsRNA (RNAi), transcriptional silencing, and sequence-independent responses to dsRNA. The outcome of the second task focuses on base pairing between small RNAs and their target RNAs and predictability of biological effects of small RNAs in animals and plants. The outcome of the last task reviews methodology, siRNA pools, and movement of small RNAs in plants. Potential transfer of small RNAs between species and circulating miRNAs in mammals is described in the final chapter.

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“…In addition to AGO and RdRP proteins, the worm RDVI also requires some components, such as RSD-2 and DRH-1, that are not conserved in plants or insects. RSD-2 is a novel protein known to contribute to chromosomal functions probably through facilitating the accumulation of secondary siRNAs (39,40). DRH-1 is a putative DEAD box RNA helicase that shares significant sequence homology with RIG-I, a mammalian cytosolic virus sensor in interferon-mediated antiviral immunity (32,41).…”

mentioning

confidence: 99%

Characterization of Virus-Encoded RNA Interference Suppressors in Caenorhabditis elegans

Guo

2013

J Virol

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In fungi, plants, and invertebrates, antiviral RNA interference (RNAi) directed by virus-derived small interfering RNAs (siRNAs) represents a major antiviral defense that the invading viruses have to overcome in order to establish infection. As a counterdefense mechanism, viruses of these hosts produce diverse classes of proteins capable of suppressing the biogenesis and/or function of viral siRNAs. This RNA-directed viral immunity (RDVI) in the nematode Caenorhabditis elegans is known to exhibit some unique features. Currently, little is known about viral suppression of RNAi in C. elegans. Here, we show that ectopic expression of the B2 protein encoded by Flock House virus (FHV) suppresses RNAi induced by either long double-stranded RNA (dsRNA) or an FHV-based replicon and facilitates the natural infection of C. elegans by Orsay virus but is not active against RNA silencing mediated by microRNAs. We report the development of an assay for the identification of viral suppressor of RNAi (VSR) in C. elegans based on the suppression of a viral replicon-triggered RDVI by ectopic expression of candidate proteins. No VSR activity was detected for either of the two Orsay viral proteins proposed previously as VSRs. We detected, among the known heterologous VSRs, VSR activity for B2 of Nodamura virus but not for 2b of tomato aspermy virus, p29 of fungus-infecting hypovirus, or p19 of tomato bushy stunt virus. We further show that, unlike that in plants and insects, FHV B2 suppresses worm RDVI mainly by interfering with the function of virus-derived primary siRNAs.

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The Caenorhabditis elegans RDE-10/RDE-11 Complex Regulates RNAi by Promoting Secondary siRNA Amplification

Cited by 53 publications

References 37 publications

Antiviral RNA Silencing Initiated in the Absence of RDE-4, a Double-Stranded RNA Binding Protein, in Caenorhabditis elegans

Antiviral RNA Silencing Initiated in the Absence of RDE-4, a Double-Stranded RNA Binding Protein, in Caenorhabditis elegans

Literature review of baseline information to support the risk assessment of RNAi‐based GM plants

Characterization of Virus-Encoded RNA Interference Suppressors in Caenorhabditis elegans

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