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Circularization of flavivirus genomic RNA inhibits de novo translation initiation

Sanford, Thomas J, Mears, Harriet V, Fajardo, Teodoro, Locker, Nicolas and Sweeney, Trevor R (2019) Circularization of flavivirus genomic RNA inhibits de novo translation initiation Nucleic Acids Research, 47 (18). pp. 9789-9802.

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Abstract

Members of the Flaviviridae family, including dengue virus (DENV) and yellow fever virus, cause serious disease in humans, whilst maternal infection with Zika virus (ZIKV) can induce microcephaly in newborns. Following infection, flaviviral RNA genomes are translated to produce the viral replication machinery but must then serve as a template for the transcription of new genomes. However, the ribosome and viral polymerase proceed in opposite directions along the RNA, risking collisions and abortive replication. Whilst generally linear, flavivirus genomes can adopt a circular conformation facilitated by long-range RNA–RNA interactions, shown to be essential for replication. Using an in vitro reconstitution approach, we demonstrate that circularization inhibits de novo translation initiation on ZIKV and DENV RNA, whilst the linear conformation is translation-competent. Our results provide a mechanism to clear the viral RNA of ribosomes in order to promote efficient replication and, therefore, define opposing roles for linear and circular conformations of the flavivirus genome.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Sanford, Thomas J
Mears, Harriet V
Fajardo, Teodoro
Locker, NicolasN.Locker@surrey.ac.uk
Sweeney, Trevor R
Date : 8 August 2019
DOI : 10.1093/nar/gkz686
Copyright Disclaimer : © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Depositing User : Clive Harris
Date Deposited : 30 Oct 2019 12:08
Last Modified : 30 Oct 2019 12:08
URI: http://epubs.surrey.ac.uk/id/eprint/852991

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