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Cited by 193

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Uptake of Extracellular Double-Stranded RNA by SID-2

Open access
McEwan, Deborah L., Weisman, Alexandra S., Hunter, Craig P.·2012·Molecular Cell

Abstract

Summary Ingested dsRNAs trigger RNA interference (RNAi) in many invertebrates including the nematode Caenorhabditis elegans. Here we show that the C. elegans apical intestinal membrane protein SID-2 is required in C. elegans for the import of ingested dsRNA and, when expressed in Drosophila S2 cells, SID-2 enables the uptake of dsRNAs. SID-2-dependent dsRNA transport requires an acidic extracellular environment and is selective for dsRNAs with at least 50 base pairs. Through structure-function analysis, we identify several SID-2 regions required for this activity including three extracellular, positively-charged, histidines. Finally, we find that SID-2-dependent transport is inhibited by drugs that interfere with vesicle transport. Therefore, we propose that environmental dsRNAs are imported from the acidic intestinal lumen by SID-2 via endocytosis and are released from internalized vesicles in a secondary step mediated by the dsRNA-channel SID-1. Similar multistep mechanisms may underlie the widespread observations of environmental RNAi.

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Crossref · 10.1016/j.molcel.2012.07.014

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  • RNAi-mediated gene silencing in non-human primates

    Zimmermann, T. S., Lee, A. C. H., Akinc, A., Bramlage, B., Bumcrot, D., Fedoruk, M. N., Harborth, J., Heyes, J. A., Jeffs, L. B., John, M., et al. (2006) · Nature · doi:10.1038/nature04688 · Cited by 1,357 · cited 2×

    “…ligands such as cholesterol and cell-type specific antibodies mediate an initial SID-2-like step that is capable of transporting siRNAs, this model additionally clarifies why fusing therapeutic siRNAs to these ligands increases their cellular uptake (Wolfrum et al., 2007; Zimmermann et al., 2006).”

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Metadata

Authors
McEwan, D. L., Weisman, A. S., & Hunter, C. P.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2012-09
Volume
47
Issue
5
Pages
746-754
ISSN
1097-2765 (ISSN-L)
OpenAlex
W1987956537
Cited by
193
References
1
FWCI
4.88
Type
journal article
Language
en
Open access
bronze

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