Double-stranded RNA (dsRNA) triggers the silencing of genes with a matching sequence through a process called RNA interference (RNAi). Surprisingly, this sequence-specific silencing information is transported between cells, sometimes causing most tissues to be silenced even when only a single cell encounters dsRNA (systemic RNAi). Screens for systemic RNAi defective (sid) mutants identified the widely-expressed dsRNA channel SID-1 that is required for the import of dsRNA or the transported silencing signal into most tissues. Further, a small transmembrane protein SID-2 required for the import of dsRNA into the gut, and an additional complementation group,
sid-3, comprised of 15 alleles were identified. We found that cells expressing a hairpin dsRNA can export a silencing signal independent of SID-1. In wild-type animals, gfp dsRNA made in pharyngeal muscle cells can silence gfp in the pharynx and, due to the transport of a silencing signal, also in the body-wall muscles. In contrast,
sid-1 mutants, silence gfp only in the pharynx (the source of the dsRNA). However, when SID-1 was expressed only in body-wall muscles, transport from pharynx to muscle was restored and gfp was silenced in body-wall muscles. This suggests that pharyngeal cells lacking
sid-1 are able to export a dsRNA-derived gfp-specific silencing signal that is then imported into body-wall muscles through SID-1. Thus, SID-1 is not required for export of the silencing signal during RNAi. In contrast,
sid-3 appears to be required for the export of a dsRNA-derived silencing signal. When we injected single gut cells of
sid-3(
qt14) mutants with gfp dsRNA, gfp was silenced through out the gut but not in other tissues, suggesting that
sid-3 mutants fail to export a silencing signal from the gut to other tissues.
sid-3 mutant cells showed enhanced silencing when dsRNA was either expressed in them or was supplied in their environment. This suggests that inhibition of export enhances cell autonomous RNAi, perhaps due to increased availability of a silencing signal. Interestingly, when placed over a deficiency (def) that covers
sid-3, the resultant hemizygous
sid-3(
qt14)/def mutants showed a more severe defect in the transport of silencing information and had lower brood sizes than
sid-3(
qt14)/sid-3
(qt14) mutants. These results suggest that the isolated
sid-3 alleles are partial loss of function alleles and that
sid-3 null mutants may be lethal.