An evolutionarily unique viral RdRP suggests a common dual-function feature of the priming element.

Abstract

Many RNA-dependent RNA polymerases (RdRPs) encoded by RNA viruses use de novo initiation strategy to start RNA synthesis, and they usually contain a priming element (PE) to interact with template RNA and priming nucleoside triphosphate to facilitate initiation. Upon transition to elongation in dengue virus 2 (DENV2) RdRP, PE refolds and contributes to elongation complex stability by interacting with the upstream RNA duplex. However, whether this PE dual-function feature commonly exists in viral RdRPs remains elusive, as PE is highly diverse among the entire RNA virus group. Here, a more complexed PE refolding is observed in RdRP crystal structures of <i>Aspergillus fumigatus</i> polymycovirus-1 (AfuPmV-1), a polymycovirus evolutionarily connecting positive-strand and double-stranded RNA viruses. Although structural details and enzymology features are very different in transition from initiation to elongation in DENV2 and AfuPmV-1 RdRPs, what is in common is the PE dual-function feature that demonstrates functional conservation beyond sequence and structure.