Loss of the putative RNA-directed RNA polymerase RRF-3 makes C. elegans hypersensitive to RNAi.
RNA interference (RNAi) is a broadly used reverse genetics method in C. elegans. Unfortunately, RNAi does not inhibit all genes. We show that loss of function of a putative RNA-directed RNA polymerase (RdRP) of C. elegans, RRF-3, results in a substantial enhancement of sensitivity to RNAi in diverse tissues. This is particularly striking in the nervous system; neurons that are generally refractory to RNAi in a wild-type genetic background can respond effectively to interference in an rrf-3 mutant background. These data provide the first indication of physiological negative modulation of the RNAi response and implicate an RdRP-related factor in this effect. The rrf-3 strain can be useful to study genes that, in wild-type, do not show a phenotype after RNAi, and it is probably the strain of choice for genome-wide RNAi screens.
Simmer
Femke
F
Hubrecht Laboratory, Center for Biomedical Genetics, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
Tijsterman
Marcel
M
Parrish
Susan
S
Koushika
Sandhya P
SP
Nonet
Michael L
ML
Fire
Andrew
A
Ahringer
Julie
J
Plasterk
Ronald H A
RH
D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics*; D010641:Phenotype; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D012330:RNA, Double-Stranded; D012324:RNA-Dependent RNA Polymerase; C472756:RNA-directed RNA polymerase RRF-3, C elegans