Tudor domain ERI-5 tethers an RNA-dependent RNA polymerase to DCR-1 to potentiate endo-RNAi

Thivierge, Caroline; Makil, Neetha; Flamand, Mathieu N.; Vasale, Jessica J.; Mello, Craig C.; Wohlschlegel, James; Conte, Darryl; Duchaîne, Thomas F.

doi:10.1038/nsmb.2186

Cited by 58 publications

(87 citation statements)

References 40 publications

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“…ERI-9 was previously shown to be required for 26G-RNA biogenesis (Pavelec et al, 2009). Consistent with the association of RDE-8 with ERI/Dicer complex components (Duchaine et al, 2006), we found that RDE-8 also co-IPs with the SAP-domain exonuclease ERI-1b (Figure S3; Kennedy et al, 2004), which interacts with both ERI-9 and Dicer and is required for the RdRP-dependent biogenesis of 26G-RNAs (Duchaine et al, 2006; Pavelec et al, 2009; Thivierge et al, 2012). …”

Section: Resultssupporting

confidence: 82%

A Ribonuclease Coordinates siRNA Amplification and mRNA Cleavage during RNAi

Tsai

Chen

Conte

et al. 2015

Cell

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102

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SUMMARY Effective silencing by RNA-interference (RNAi) depends on mechanisms that amplify and propagate the silencing signal. In some organisms, small-interfering (si) RNAs are amplified from target mRNAs by RNA-dependent RNA polymerase (RdRP). Both RdRP recruitment and mRNA silencing require Argonaute proteins, which are generally thought to degrade RNAi targets by directly cleaving them. However in C. elegans, the enzymatic activity of the primary Argonaute, RDE-1, is not required for silencing activity. We show that RDE-1 can instead recruit an endoribonuclease, RDE-8, to target RNA. RDE-8 can cleave RNA in vitro and is needed for the production of 3′ uridylated fragments of target mRNA in vivo. We also find that RDE-8 promotes RdRP activity, thereby ensuring amplification of siRNAs. Together, our findings suggest a model in which RDE-8 cleaves target mRNAs to mediate silencing, while generating 3’ uridylated mRNA fragments to serve as templates for the RdRP-directed amplification of the silencing signal.

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Section: Resultssupporting

confidence: 82%

A Ribonuclease Coordinates siRNA Amplification and mRNA Cleavage during RNAi

Tsai

Chen

Conte

et al. 2015

Cell

Self Cite

102

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“…A genome-wide RNAi screen identified these RNAi pathway genes to act redundantly with the KSR-1 (kinase suppressor of Ras) scaffolding protein in Rasmediated excretory duct cell specification (Rocheleau et al 2008). Since DRH-3 is a component of the RdRP complex Thivierge et al 2012) required for the biogenesis of all 22G-RNAs, including those present in the complex with CSR-1 , it is most likely that DRH-3-dependent CSR-1-bound endo-siRNAs regulate a number of genes affecting developmental events, such as HSN migration and excretory duct specification.…”

Section: Discussionmentioning

confidence: 99%

Neuronal Migration Is Regulated by Endogenous RNAi and Chromatin-Binding Factor ZFP-1/AF10 in Caenorhabditis elegans

Kennedy

Grishok

2014

Genetics

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Endogenous short RNAs and the conserved plant homeodomain (PHD) zinc-finger protein ZFP-1/AF10 regulate overlapping sets of genes in Caenorhabditis elegans, which suggests that they control common biological pathways. We have shown recently that the RNAi factor RDE-4 and ZFP-1 negatively modulate transcription of the insulin/PI3 signaling-dependent kinase PDK-1 to promote C. elegans fitness. Moreover, we have demonstrated that the insulin/IGF-1-PI3K-signaling pathway regulates the activity of the DAF-16/FOXO transcription factor in the hypodermis to nonautonomously promote the anterior migrations of the hermaphroditespecific neurons (HSNs) during embryogenesis of C. elegans. In this study, we implicate the PHD-containing isoform of ZFP-1 and endogenous RNAi in the regulation of HSN migration. ZFP-1 affects HSN migration in part through its negative effect on pdk-1 transcription and modulation of downstream DAF-16 activity. We also identify a novel role for ZFP-1 and RNAi pathway components, including RDE-4, in the regulation of HSN migration in parallel with DAF-16. Therefore, the coordinated activities of DAF-16, ZFP-1, and endogenous RNAi contribute to gene regulation during development to ensure proper neuronal positioning.

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“…Interestingly, worms employ a distinct analogous signal amplification mechanism that leads to generation of secondary downstream siRNAs upon piRNA: target RNA interaction (on which more below). Despite these apparent differences in the nematode pathway, other protein factors found in Drosophila and mice have also been implied in piRNA silencing in C. elegans: tudor-domain proteins have a demonstrated role in endogenous small RNA pathways (Thivierge et al, 2011) and EKL-1 is a TDRD involved in piRNA-dependent siRNA generation (Gu et al, 2009). The C. elegans genome encodes several additional uncharacterised TDRDs and study of their involvement in the piRNA pathway should be an interesting avenue for future research.…”

Section: Piwi Proteins and Pirna Biogenesis In C Elegansmentioning

confidence: 99%

piRNAs: from biogenesis to function

2014

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Distinguishing self from non-self plays a crucial role in safeguarding the germlines of metazoa from mobile DNA elements. Since their discovery less than a decade ago, Piwi-interacting RNAs ( piRNAs) have been shown to repress transposable elements in the germline and, hence, have been at the forefront of research aimed at understanding the mechanisms that maintain germline integrity. More recently, roles for piRNAs in gene regulation have emerged. In this Review, we highlight recent advances made in understanding piRNA function, highlighting the divergent nature of piRNA biogenesis in different organisms, and discussing the mechanisms of piRNA action during transcriptional regulation and in transgenerational epigenetic inheritance.

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Tudor domain ERI-5 tethers an RNA-dependent RNA polymerase to DCR-1 to potentiate endo-RNAi

Cited by 58 publications

References 40 publications

A Ribonuclease Coordinates siRNA Amplification and mRNA Cleavage during RNAi

A Ribonuclease Coordinates siRNA Amplification and mRNA Cleavage during RNAi

Neuronal Migration Is Regulated by Endogenous RNAi and Chromatin-Binding Factor ZFP-1/AF10 in Caenorhabditis elegans

piRNAs: from biogenesis to function

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