A Structure-Function Diversity Survey of the RNA-Dependent RNA Polymerases From the Positive-Strand RNA Viruses

Jia, Hengxia; Gong, Peng

First identified in the 1950s in the mengovirus and poliovirus (PV) related studies (Reich et al., 1961 (Reich et al., , 1962 , the RNA-dependent RNA polymerases (RdRPs) encoded by the RNA viruses catalyze the RNA synthesis from RNA templates, and are responsible for the viral genome replication and transcription processes. As the essential and the most conserved protein from the RNA viruses, the RdRPs are attractive systems both for understanding the fundamentals of nucleic acid synthesis and for developing antiviral strategies. Each RdRP contains a catalytic module (or catalytic core) with an overall architecture resembling an encircled human right hand that is composed of the palm, fingers, and thumb domains (Hansen et al., 1997; Ago et al., 1999; Bressanelli et al., 1999; Lesburg et al., 1999) . The size of the catalytic module is typically about 50 and 70 kilo-Dalton (kD) for primer-dependent and de novo RdRPs, respectively, regarding the RdRP initiation mode (Lesburg et al., 1999; Thompson and Peersen, 2004) . However, the size of the RdRP protein could reach 240-450 kD (Kinsella et al., 2004; Liang et al., 2015; Gerlach et al., 2015) , often due to the requirement of incorporating other functional modules or as a result of coevolution with different host species. To some extent, the conservation of the catalytic module and the diversity of the full-length RdRP protein are two important aspects in understanding this unique class of polymerases. In this review, we surveyed all 46 RdRP-sequence available virus families listed in the International Committee on Virus Taxonomy (ICTV) 1 2018b collection from the positive-strand RNA virus category [ssRNA(+) in the ICTV genome composition assignment] and tend to provide an RdRP reference map based on known information of RdRP structure and function. The main purpose of this work is to place the current knowledge of these RdRPs in a broader context and to facilitate future studies in RdRPs with representative primary structure and/or with distinct functions beyond the catalytic module, thereby help improve the overall understanding of RdRP structure, function, and evolution. Based on sequence availability in the United States National Center for Biotechnology Information (NCBI) database 2 , one representative RdRP amino acid sequence was chosen for each virus family by giving the priority to the ICTV-suggested type species ( Table 1) .