In Caenorhabditis elegans, the introduction of double-stranded RNA Triggers
sequence-specific generic interference (RNAi) that is transmitted to offsp
ring. The inheritance properties associated with this phenomenon were exami
ned. Transmission of the interference effect occurred through a dominant ex
tragenic agent. The wild-type activities of the RNAi pathway genes rde-1 an
d rde-4 were required for the formation of this interfering agent but were
not needed for interference thereafter. In contrast, the rde-2 and mut-7 ge
nes were required downstream for interference. These findings provide evide
nce for germ line transmission of an extragenic sequence-specific silencing
factor and implicate rde-1 and rde-4 in the formation of the inherited age
nt.