Abstract:
RNA silencing is an evolutionarily conserved system that
functions as an antiviral mechanism in higher plants and
insects. To counteract RNA silencing, viruses express
silencing suppressors that interfere with both siRNA- and
microRNA-guided silencing pathways. We used comparative
in vitro and in vivo approaches to analyse the molecular
mechanism of suppression by three well-studied
silencing suppressors. We found that silencing suppressors
p19, p21 and HC-Pro each inhibit the intermediate
step of RNA silencing via binding to siRNAs, although the
molecular features required for duplex siRNA binding
differ among the three proteins. None of the suppressors
affected the activity of preassembled RISC complexes.
In contrast, each suppressor uniformly inhibited the
siRNA-initiated RISC assembly pathway by preventing
RNA silencing initiator complex formation
