RNA interference (RNAi) is a phylogenetically conserved gene regulation mechanism that modulates a wide variety of biological functions through the production of small non-coding RNAs. One of the major natural functions of RNAi is antiviral which has been documented in fungus, plant and invertebrate. Although RNAi directed viral immunity (RDVI) has not been reported in vertebrates our recent study on worm gene
drh-1 has established a genetic link between mammalian cytosolic viral innate immunity and worm RDVI. Since both vertebrate and worm are known to encode single dicer, the key enzyme responsible for the biogenesis of several classes of small RNAs, our study thus suggested that a unique antiviral gene is shared in between single-dicer organisms.
drh-1 (dicer-related RNA helicase 1) was originally identified as an RNAi gene which encodes a protein with physical interaction with RDE-4, a dsRNA binding protein whose insect homologue is known to play important role in RDVI.
drh-1 was implicated in worm RDVI in a genetic screen aimed to isolate novel factors of worm RDVI. Surprisingly, in contrast to
rde-1 (encoding an Argonaut protein required for classical RNAi) and
rde-4,
drh-1 appeared to be dispensable in RNAi targeting either endogenous genes, such as
unc-22 and
skn-1, or a GFP transgene. This viral transcript-specific function of
drh-1 can not be attributed to its role in viral siRNA (viRNA) biogenesis since viRNA production is not compromised in
drh-1 deficient mutant.
drh-1 does not function in a viRNA-specific manner either since siRNA of non-viral origin failed to mediate virus silencing in the absence of
drh-1. Our recent study further demonstrated that silencing of non-viral transcripts triggered by viRNA still occur in the absence of
drh-1. Since
drh-1 is not required for production of any known endogenous small RNA species and the
drh-1 null mutant is free of any developmental defects, these observations altogether strongly suggested that
drh-1 specifically targets viral transcript for function irrespective of the origin of siRNA effectors.