In C. elegans , very small quantities of dsRNA are sufficient to generate RNA interference not only in the animal that is exposed to dsRNA but also in subsequent generations (1, 2). These findings indicate that amplification and inheritance of a silencing agent(s) (such as siRNA) are important to the mechanism of RNAi. P-granules, the worm equivalent of germ granules, are expressed in the maternal germline, deposited into early embryos and are implicated in translational regulation of maternal mRNAs. Therefore, we hypothesized that the germline P-granules of C. elegans may be important for the transmission of a silencing factor and hence for RNAi. An examination of mutations in known P-granule components revealed that the PGL-1 protein is required for RNAi. siRNAs failed to accumulate in
pgl-1 mutant worms exposed to dsRNA targeting a maternal mRNA, while siRNAs appeared to accumulate in the embryos of wild-type worms. Remarkably, animals challenged with dsRNA targeting zygotic mRNAs expressed in somatic tissues produced progeny with a reduced penetrance of RNAi phenotypes. These data are consistent with the hypothesis that PGL-1 may be important for efficient transmission of a silencing agent to the progeny of animals exposed to dsRNA. PGL-1 encodes a protein with an RGG-box found in RNA-binding proteins and is required for fertility in C. elegans (3). An attractive scenario is that PGL-1 interacts with and transmits siRNA to the progeny of animals exposed to dsRNA. Alternatively, PGL-1 may regulate the activity of the RNAi pathway by modulating the accessibility, localization or expression of RNAi pathway components or intermediates. We will present our recent efforts to elucidate the function of PGL-1 in RNAi and the relationship to the role of PGL-1 in development. 1) Fire et al. (1998) Nature 391:806-811 2) Grishok, Tabara and Mello (2000) Science 287:2494-2497 3) Kawasaki et al. (1998) Cell 94:635-645 This work is funded by National Institutes of Health grants GM058800 (to C.C.M.) and GM063348 (to D.C.)