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Title: Identification of a conserved RNA-dependent RNA polymerase (RdRp)-RNA interface required for flaviviral replication
Authors: Kenneth Hodge
Chairat Tunghirun
Maliwan Kamkaew
Thawornchai Limjindaporn
Pa Thai Yenchitsomanus
Sarin Chimnaronk
Mahidol University
Faculty of Medicine, Siriraj Hospital, Mahidol University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 12-Aug-2016
Citation: Journal of Biological Chemistry. Vol.291, No.33 (2016), 17437-17449
Abstract: © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. Dengue virus, an ∼10.7-kb positive-sense RNA virus, is the most common arthropod-communicated pathogen in the world. Despite dengue's clear epidemiological importance, mechanisms for its replication remain elusive. Here, we probed the entire dengue genome for interactions with viral RNA-dependent RNA polymerase (RdRp), and we identified the dominant interaction as a loop-forming ACAG motif in the 3' positive-stranded terminus, complicating the prevailing model of replication. A subset of interactions coincides with known flaviviral recombination sites inside the viral protein-coding region. Specific recognition of the RNA element occurs via an arginine patch in the C-terminal thumb domain of RdRp. We also show that the highly conserved nature of the consensus RNA motif may relate to its tolerance to various mutations in the interacting region of RdRp. Disruption of the interaction resulted in loss of viral replication ability in cells. This unique RdRp-RNA interface is found throughout flaviviruses, implying possibilities for broad disease interventions.
ISSN: 1083351X
Appears in Collections:Scopus 2016-2017

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