Structural basis for the regulatory function of a complex zinc-binding domain in a replicative arterivirus helicase resembling a nonsense-mediated mRNA decay helicase

Deng, Zengqin; Lehmann, Kathleen C.; Li, Xiaorong; Feng, Chong; Wang, Guoqiang; Zhang, Qi; Qi, Xiaoxuan; Yu, Lin; Zhang, Xingliang; Feng, Wenhai; Wu, Wei; Gong, Peng; Tao, Ye; Posthuma, Clara C.; Snijder, Eric J.; Gorbalenya, Alexander E.; Chen, Zhongzhou

Despite this recent progress, the two central subunits of the nidovirus replicase, the RdRp and the unique ZBDcontaining RNA helicase, have remained poorly characterized, also due to the lack of structural information. Remarkably, our present analysis of the arterivirus helicase structure revealed a number of important similarities with Upf1 helicases, eukaryotic enzymes involved in quality control of RNAs through multiple pathways, including nonsense-mediated mRNA decay (54) (55) (56) . In contrast to the ExoN-driven control of replication fidelity (see above), the possibility of post-transcriptional quality control of nidovirus mRNAs has not been considered thus far. Yet, replicase ORF1ab is extremely large (from 3175 to >7000 codons) and its correct expression by translation of the viral genome is a critical first step in the production of the enzymes directing genome replication and expression. Therefore, our study not only provides the first insights into the structural basis for nidovirus RNA helicase function, but also creates a basis to propose a role for this protein in the posttranscriptional quality control of viral mRNAs. This role may be common to all nidoviruses, regardless of their genomes size, which would distinguish it from the ExoN-based proofreading mechanism that appears to be restricted to nidoviruses with a >20 kb genome. On the time scale of nidovirus evolution, the acquisition of Figure 2A . Note that the DNA in Figure 5C was extracted from the complex structure of DNA-bound state.