On the nature of in vivo requirements for<i>rde-4</i>in RNAi and developmental pathways in<i>C. elegans</i>

Blanchard, Daniel; Parameswaran, Poornima; Lopez-Molina, Javier; Gent, Jonathan I.; Saynuk, Jamie Fleenor; Fire, Andrew

doi:10.4161/rna.8.3.14657

Cited by 24 publications

(25 citation statements)

References 48 publications

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“…In the above study of induced transport of RNA between cells (Timmons et al, 2003), such a control is simply not possible because the observed effect requires the import of unrelated dsRNA, which requires SID-1. In two other studies, when the rde-4 (+) gene was expressed under the control of the muscle-specific myo-3 promoter, apparently rde-4 -independent silencing was observed in non-muscle cells in response to ingested dsRNA (Jose et al, 2011) or in the next generation in response to injected dsRNA (Blanchard et al, 2011). Similar inability to control for misexpression from promoters makes the interpretation of these observations provisional.…”

Section: Cautionary Talesmentioning

confidence: 94%

“…Furthermore, the ability to detect silencing by mobile RNAs could be obscured by other competing RNA silencing pathways that are active within a cell (Lee et al, 2006, Zhuang and Hunter, 2012). Mosaic analyses were used to characterize silencing by mobile RNAs derived from ingested dsRNA (Jose et al, 2011) and injected dsRNA (Blanchard et al, 2011), but limitations of this experimental approach weaken conclusions (see section on `Cautionary tales'). Finally, despite the ability to trigger gene silencing using dsRNA ingestion in many animals, we have minimal knowledge of the mechanism of gene silencing by mobile RNAs generated from such triggers because it is difficult to distinguish the effects of imported dsRNA from those of dsRNA-derived mobile RNAs.…”

Section: Gene Regulationmentioning

confidence: 99%

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Movement of regulatory RNA between animal cells

Jose

2015

Genesis

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Summary Recent studies suggest that RNA can move from one cell to another and regulate genes through specific base-pairing. Mechanisms that modify or select RNA for secretion from a cell are unclear. Secreted RNA can be stable enough to be detected in the extracellular environment and can enter the cytosol of distant cells to regulate genes. Mechanisms that import RNA into the cytosol of an animal cell can enable uptake of RNA from many sources including other organisms. This role of RNA is akin to that of steroid hormones, which cross cell membranes to regulate genes. The potential diagnostic use of RNA in human extracellular fluids has ignited interest in understanding mechanisms that enable the movement of RNA between animal cells. Genetic model systems will be essential to gain more confidence in proposed mechanisms of RNA transport and to connect an extracellular RNA with a specific biological function. Studies in the worm C. elegans and in other animals have begun to reveal parts of this novel mechanism of cell-to-cell communication. Here, I summarize the current state of this nascent field, highlight the many unknowns, and suggest future directions.

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Section: Cautionary Talesmentioning

confidence: 94%

Section: Gene Regulationmentioning

confidence: 99%

Movement of regulatory RNA between animal cells

Jose

2015

Genesis

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“…Mutations in rde-4 have been associated with decreased life span (Welker et al 2007;Mansisidor et al 2011) and increased sensitivity to oxidative stress (Mansisidor et al 2011) and temperature (Blanchard et al 2011). An increase in stress sensitivity and reduced life span of rde-4 mutants has been attributed to the upregulation of pdk-1 (Mansisidor et al 2011).…”

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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“…Mutants and biochemical analyses support a model where RDE-4 dimerizes through the C-terminal domain; dimers cooperatively bind long dsRNA, interacts with Dicer through the linker region, and forms a complex initiating the RNAi together with Dicer, RDE-1, and DRH-1/2 Tabara et al, 2002;Parker et al, 2006;Parker et al, 2008;Blanchard et al, 2011;Chiliveri and Deshmukh, 2014). The presence of an Argonaute protein in the complex suggests that in exo-RNAi, dsRNA recognition, processing into siRNA and loading of the Argonaute-containing effector complex is integrated in a one complex.…”

Section: Dsrbps -Rde-4 and Homologsmentioning

confidence: 99%

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

Pačes

Nič²,

Novotný³

et al. 2017

EFS3

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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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On the nature of in vivo requirements forrde-4in RNAi and developmental pathways inC. elegans

Cited by 24 publications

References 48 publications

Movement of regulatory RNA between animal cells

Movement of regulatory RNA between animal cells

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

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

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