title: A Structural Overview of RNA-Dependent RNA Polymerases from the Flaviviridae Family.
abstract: RNA-dependent RNA polymerases (RdRPs) from the Flaviviridae family are representatives of viral polymerases that carry out RNA synthesis through a de novo initiation mechanism. They share a ≈ 600-residue polymerase core that displays a canonical viral RdRP architecture resembling an encircled right hand with palm, fingers, and thumb domains surrounding the active site. Polymerase catalytic motifs A-E in the palm and motifs F/G in the fingers are shared by all viral RdRPs with sequence and/or structural conservations regardless of the mechanism of initiation. Different from RdRPs carrying out primer-dependent initiation, Flaviviridae and other de novo RdRPs utilize a priming element often integrated in the thumb domain to facilitate primer-independent initiation. Upon the transition to the elongation phase, this priming element needs to undergo currently unresolved conformational rearrangements to accommodate the growth of the template-product RNA duplex. In the genera of Flavivirus and Pestivirus, the polymerase module in the C-terminal part of the RdRP protein may be regulated in cis by the N-terminal region of the same polypeptide. Either being a methyltransferase in Flavivirus or a functionally unclarified module in Pestivirus, this region could play auxiliary roles for the canonical folding and/or the catalysis of the polymerase, through defined intra-molecular interactions.
authors.affiliation: Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, No. 44 Xiao Hong Shan, Wuchang District, Wuhan 430071, China. wujiqin2010@163.com.|State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China. wujiqin2010@163.com.|University of Chinese Academy of Sciences, Beijing 100049, China. wujiqin2010@163.com.
authors.forename: Jiqin
authors.initials: J
authors.lastname: Wu
authors.affiliation: Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, No. 44 Xiao Hong Shan, Wuchang District, Wuhan 430071, China. liuweichi1990@163.com.|State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China. liuweichi1990@163.com.|University of Chinese Academy of Sciences, Beijing 100049, China. liuweichi1990@163.com.
authors.forename: Weichi
authors.initials: W
authors.lastname: Liu
authors.affiliation: Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, No. 44 Xiao Hong Shan, Wuchang District, Wuhan 430071, China. gongpeng2001@yahoo.com.|State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China. gongpeng2001@yahoo.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Gong
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D018067:Flaviviridae / Q000201:enzymology*; D008969:Molecular Sequence Data; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry* / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase
keywords: Flaviviridae; RNA-dependent RNA polymerase; catalytic motif; de novo initiation; elongation; in cis regulation