The uptake of double-stranded RNA (dsRNA) from the medium is the mainstay of many an RNA silencing strategy, but what is the mechanism by which animal cells take up these macromolecules? It has been difficult to address this directly because in some cases, cells seem to take up dsRNA directly from the medium, yet in others there can be cell-to-cell transfer.
Because Drosophila cells can take up dsRNA but do not transport it between cells, Saleh et al. used Drosophila tissue culture cells to characterize the uptake pathway. In a genome-wide screen for participants, components of the receptor-mediated endocytosis pathway were found to predominate. The receptors involved were members of the pattern-recognition receptor family, which is important in innate immunity and antimicrobial defense. Furthermore, similar mechanisms are likely to be widespread in evolution: Knockdown of orthologous endocytic players in nematodes also prevented RNA interference. How incoming dsRNA is diverted from the endocytic pathway so as to avoid degradation in lysosomes remains a mystery. -- SMH
Nat. Cell Biol. 8, 793 (2006).
