Program of the 2004 East Coast Worm Meeting - Caenorhabditis ...

13. The germ granule protein PGL-1 is required for efficient RNA interference
Darryl Conte Jr. 1 , Yingdee Unhavathaya 1 , Craig C. Mello 1,2
1Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA
01605
2Howard Hughes Medical Institute
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.)