RNA-mediated interference (RNAi) is a rapid and efficient method for disrupting a specific gene in many organisms, especially C. elegans . Although RNAi is efficient in almost all tissues, neurons of C. elegans show resistance to RNAi. To investigate functions of genes expressed in neurons efficiently, we have engaged to develop the RNAi system effective even in neurons. Recently, many genes involved in the RNAi mechanism have been identified. RNA dependent RNA polymerase (RdRP) plays a critical role in RNAi mechanism. C. elegans has four RdRP genes (
ego-1 ,
rrf-1 ,
rrf-2 , and
rrf-3 ). Although
ego-1 and
rrf-1 are indispensable for RNAi in germline and somatic cells, respectively,
rrf-2 and
rrf-3 deletion mutants have no defects in RNAi. Since it is reported that mutation in
rrf-3 increases RNAi efficiency in somatic cells, there is a possibility that RNAi is also effective to neuronal expressed genes in
rrf-3 worms. In this meeting, we reporte RNAi efficiency of
rrf-3 deletion mutants in the hypodermis at embryonic stage and in neurons at postembryonic stage. We selected
let-502 ,
unc-18 and
unc-33 genes as markers for examining RNAi efficiency at the embryonic and the postembryonic stages. By feeding RNAi of
let-502 , we found that progenies from wild type worms show a Dpy phenotype, similar to weak allele of
let-502 , whereas that most of
rrf-3 progenies exhibit late embryonic or larval lethal phenotype, suggesting that RNAi efficiency increases in
rrf-3 during embryogenesis. Feeding RNAi of
unc-18 and
unc-33 to
rrf-3 mutant worms produced Unc progenies clearly at early larva stage. However, the Unc phenotype of
unc-18 (RNAi) was restored at larval stages, resulting that adult RNAi animals showed Non-Unc phenotype. These results suggest that in
rrf-3 animals RNAi is effective in neuron, but that RNAi in neuron is incomplete. To develop a complete neural RNAi system, now we are screening mutants in which RNAi is effective in neurons.