Is it just by viruses or are there other means by which it gets into cells, such as plasmid uptake?

  • $\begingroup$ Artificially or naturally? $\endgroup$
    – Superbest
    Nov 9 '14 at 3:01

Besides viral infections there are different pathways for cells to take up dsRNA. Inside the cells these dsRNA are processed by Dicer which processes these RNAs into small interfering RNA, which play an important role in the regulation of gene activity.

These pathways have mostly been researched in Drosophila and C. elegans, I am indicating where evidence for them in humans is available. The different possibilities for the uptake are:

  • Uptake via transmembrane proteins: In C. elegans two different transmembrane proteins have been discovered which passively transport dsRNA into the cells. They are called SID-1 and SID-2 (systemic RNA-interference defective protein), at least for SID-1 a homologue exists in humans as well. These receptors are important for the uptake of systemic (produced by the own organism) dsRNA. See references 1-3 for details.
  • Uptake via Endocytosis: In drosophila cells active transport happens through the scavenger receptors SR-CI and Eater. They bind the dsRNA and are then internalized. Knockdown of these genes inhibited the import of dsRNA and inhibited the endocytosis mediated knockdown of genes. This process seems to be evolutionary conserved, as knockdown of the orthologous genes in C. elegans led to similar results. This mechanism seems to be more important for the uptake of environmental dsRNA. See references 4 and 5 for more details.
  • Uptake via Phagocytosis: At least for drosophila, there is evidence for a phagocytosis mediated uptake mechanism, which is independent of endocytosis. See reference 6 for details.


  1. SID-1 is a dsRNA-selective dsRNA-gated channel.
  2. Uptake of extracellular double-stranded RNA by SID-2
  3. RNA interference: a mammalian SID-1 homologue enhances siRNA uptake and gene silencing efficacy in human cells.
  4. The endocytic pathway mediates cell entry of dsRNA to induce RNAi silencing.
  5. Double-stranded RNA Is Internalized by Scavenger Receptor-mediated Endocytosis in Drosophila S2 Cells
  6. A phagocytic route for uptake of double-stranded RNA in RNAi
  • $\begingroup$ SID-1 looks interesting. Do you think there's a size limit or would it take up long dsRNA molecules? $\endgroup$
    – user137
    Oct 28 '14 at 14:17
  • $\begingroup$ @user137 This paper suggests that very different length (they tested from siRNA length to 500bp) are taken up. The longer the dsRNA gets, the more effective (meaning smaller concentrations of the dsRNA outside the cells lead to a downregulation) the process seems to be. $\endgroup$
    – Chris
    Oct 28 '14 at 15:48

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