Uptake of Extracellular Double-Stranded RNA by SID-2

McEwan, Deborah L.; Weisman, Alexandra S.; Hunter, Craig P.

doi:10.1016/j.molcel.2012.07.014

Cited by 176 publications

(183 citation statements)

References 29 publications

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“…Consistent with this observation, endogenous plant miRNAs showed no significant accumulation in WCR larvae fed on corn roots (Zhang et al 2012), further supporting the observation that exogenous small RNAs are not taken up efficiently or are less stable via oral delivery. Interestingly, in C. elegans, SID-2-dependent dsRNA transport is required for eRNAi and exhibits size dependency by facilitating the uptake of dsRNA longer than 50 bp (McEwan et al 2012). In spite of the obvious similarity in length requirement for the uptake of dsRNA in WCR and C. elegans, the SID-2 ortholog has not been identified in WCR (Miyata et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Environmental RNAi in herbivorous insects

Ivashuta

Zhang

Wiggins

et al. 2015

RNA

113

132

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Environmental RNAi (eRNAi) is a sequence-specific regulation of endogenous gene expression in a receptive organism by exogenous double-stranded RNA (dsRNA). Although demonstrated under artificial dietary conditions and via transgenic plant presentations in several herbivorous insects, the magnitude and consequence of exogenous dsRNA uptake and the role of eRNAi remains unknown under natural insect living conditions. Our analysis of coleopteran insects sensitive to eRNAi fed on wild-type plants revealed uptake of plant endogenous long dsRNAs, but not small RNAs. Subsequently, the dsRNAs were processed into 21 nt siRNAs by insects and accumulated in high quantities in insect cells. No accumulation of host plantderived siRNAs was observed in lepidopteran larvae that are recalcitrant to eRNAi. Stability of ingested dsRNA in coleopteran larval gut followed by uptake and transport from the gut to distal tissues appeared to be enabling factors for eRNAi. Although a relatively large number of distinct coleopteran insect-processed plant-derived siRNAs had sequence complementarity to insect transcripts, the vast majority of the siRNAs were present in relatively low abundance, and RNA-seq analysis did not detect a significant effect of plant-derived siRNAs on insect transcriptome. In summary, we observed a broad genome-wide uptake of plant endogenous dsRNA and subsequent processing of ingested dsRNA into 21 nt siRNAs in eRNAi-sensitive insects under natural feeding conditions. In addition to dsRNA stability in gut lumen and uptake, dosage of siRNAs targeting a given insect transcript is likely an important factor in order to achieve measurable eRNAi-based regulation in eRNAi-competent insects that lack an apparent silencing amplification mechanism.

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Section: Introductionmentioning

confidence: 99%

Environmental RNAi in herbivorous insects

Ivashuta

Zhang

Wiggins

et al. 2015

RNA

113

132

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“…SID-2 is a gut-specific receptor and mediates dietary uptake of sRNAs in a SID-1-dependent manner 83 via endocytosis. 84 SID-5 appears to be required for releasing sRNAs from endosomes, 85 further supporting the critical role of endocytosis in sRNA uptake. SID-1 homologues and SID-like (SIL) proteins have been found in other insects, 86,87 but no SID-2 proteins have been discovered.…”

Section: Do Srnas Cross the Digestive Tract Barrier?mentioning

confidence: 80%

Uptake and impact of natural diet-derived small RNA in invertebrates: Implications for ecology and agriculture

Chan

Snow

2016

RNA Biology

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The putative transfer and gene regulatory activities of diet-derived small RNAs (sRNAs) in ingesting animals are still debated. The existence of natural uptake of diet-derived sRNA by invertebrate species could have significant implication for our understanding of ecological relationships and could synergize with efforts to use RNA interference (RNAi) technology in agriculture. Here, we synthesize information gathered from studies in invertebrates using natural or artificial dietary delivery of sRNA and from studies of sRNA in vertebrate animals and plants to review our current understanding of uptake and impact of natural dietderived sRNA on invertebrates. Our understanding has been influenced and sometimes confounded by the diversity of invertebrates and ingested plants studied, our limited insights into how gene expression may be modulated by dietary sRNAs at the mechanistic level, and the paucity of studies focusing directly on natural uptake of sRNA. As such, we suggest 2 strategies to investigate this phenomenon more comprehensively and thus facilitate the realization of its potentially broad impact on ecology and agriculture in the future.

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“…97,98 Sid-2 is a single-pass transmembrane protein which is located at the luminal membrane of the intestine, 99 and is also involved in the absorption of ingested ds RNA. 100 According to the current working hypothesis, Sid-2 binds long dsRNA first for endocytosis then the dsRNA is presented to Sid-1. For an efficient uptake of dsRNA to the intestinal cell cytoplasm, the activation of Sid-1 by Sid-2 is inevitable.…”

Section: Required Amount Of Mirnas For Biological Activitymentioning

confidence: 99%

Potential relevance of microRNAs in inter-species epigenetic communication, and implications for disease pathogenesis

et al. 2016

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MicroRNAs are short non-protein coding RNA molecules involved in the epigenetic regulation of gene expression. Recently, extracellular microRNAs have been described in body fluids that might enable epigenetic communication between distant tissues. Being highly conserved molecules, exogenous xenomicroRNAs from different species could affect gene expression in the host even in a cross-kingdom fashion. Several data underline the relevance of microRNA-mediated communication between virus and host, and there are some experimental data showing that plant-or animal-derived dietary microRNAs might have gene expression modulating activity in humans. Milk-derived microRNAs might be involved in the "epigenetic priming" of the baby. Exogenous microRNAs might be hypothesized to be implicated in disease pathogenesis, e.g. in tumors. Major questions remain to be addressed including the amount of xeno-microRNAs needed for biological action or routes for microRNA delivery. In this brief review, experimental data and hypotheses on the potential pathogenic inter-species relevance of microRNA are presented.Abbreviations: AGO2, Argonaute-2 protein; dsRNA, double stranded RNA; FoxO1, forkhead box class O1A; FOXP3, forkhead box P3; HDL, high density lipoprotein; LDL, low density lipoprotein; LDLRAP1, low-density lipoprotein receptor adapter protein 1; miRNA, miR, microRNA; mTORC1, mechanistic target of rapamycin complex 1; premiRNA, precursor microRNA; pri-miRNA, primary microRNA; RISC, RNA-induced silencing complex; RUNX2, runt related transcription factor 2; siRNA, small interfering RNA; TCF7, transcription factor 7; TLR, Toll-like receptor; Treg, regulatory T-cell; ZEB1, zinc finger E-box binding homeobox 1

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Uptake of Extracellular Double-Stranded RNA by SID-2

Cited by 176 publications

References 29 publications

Environmental RNAi in herbivorous insects

Environmental RNAi in herbivorous insects

Uptake and impact of natural diet-derived small RNA in invertebrates: Implications for ecology and agriculture

Potential relevance of microRNAs in inter-species epigenetic communication, and implications for disease pathogenesis

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