What lessons can be learned from the use of RNAi in
model organisms in relation to a ‘real-life’ biological problem,
such as crop protection against insect pests? Uptake
of dsRNA in C. elegans has been studied by genetic
analysis. A mutant has been identified that is impaired
in its ability to mediate a systemic RNAi response when
dsRNA is delivered orally [15]. The gene identified,
systemic RNA interference deficient-1 (sid-1), is essential
and sufficient to mediate systemic RNAi effect in C.elegans.
When expressed in Drosophila S2 cells, sid-1 enhanced the ability of S2 cells to uptake dsRNA at sub-optimal dsRNA
concentrations. The gene is predicted to encode an elevenhelix
transmembrane channel protein that is expressed on
the cell surface and enables uptake of dsRNAs, thereby
mediating a systemic RNAi effect. Further potential mechanisms
for RNA transport have been suggested by the
recent identification of a further C. elegans dsRNA uptake
mutant, sid-2 [16]. sid-2 mutants are unable to mediate an
RNAi response when fed bacteria expressing specific
dsRNAs. The sid-2 gene product has been identified as a
gut-specific transmembrane protein with a single transmembrane
region. To demonstrate functionality, a related
nematode, Caenorhabditis briggsae, which is defective in
uptake of dsRNA from the gut lumen, was transformed
with C. elegans sid-2, and a systemic RNAi phenotype was
restored [16]. This demonstration of the complexity of
RNAi-uptake mechanisms and the systemic spread of an
RNAi signal in a single organism needs to be bourne in
mind when considering RNAi in insects.