RNA interference (RNAi) is a conserved pathway that likely had an ancestral role in defending genomes against selfish elements and viruses. Modern day invertebrates still rely on RNAi for viral defense, while in most vertebrates, the interferon pathway is the primary means of fighting a viral infection. However, a role for RNAi in vertebrate innate immunity has not been ruled out. A key player in RNAi is Dicer, a multidomain, ribonuclease (RNase) III family member that cleaves viral or endogenous dsRNA into microRNAs (miRNAs) or small interfering RNAs (siRNA). While Dicer binds and cleaves viral dsRNA to trigger antiviral RNAi in invertebrates, the recognition of viral dsRNA during a vertebrate interferon response is performed by RIG-I-like Receptors (RLRs). Despite differences in their domain organization and functions, Dicer and RLRs share a conserved DExD/H-box helicase domain. The conservation of Dicer’s helicase domain with that of RLRs suggests this domain functioned in antiviral defense in a common ancestor, and it is fascinating to imagine the host-virus arms race that led to the distinctly different innate immune pathways of extant vertebrates and invertebrates. C. elegans is of keen interest in this regard because its single encoded Dicer functions in complex with an RLR homolog to mediate an antiviral RNAi response. The antiviral complex in C. elegans includes Dicer (DCR-1), the RIG-I ortholog called Dicer-Related Helicase-1 (DRH-1), and a dsRNA binding protein called RNAi deficient-4 (RDE-4). Here you can see the cryo-EM structure of DRH-1 helicase and C-terminal domain from C.elegans bound to dsRNA (PDB code: 8T5S)

#molecularart #rnai #dicer #helicase #drh1 #celegans #interference #cryoem

Structure rendered with @proteinimaging, post-processed with @stylar.ai_official and depicted with @corelphotopaint