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nature portfolio privacy policy individual research grant nature communications advertising laboratory animal research long-range pair-wise interactions long-range rna–rna interactions supplementary data file supplementary information files performed library preparation pair-wise experimental data reprints long-range interaction data xian jun loh materials research nature 496 nature 460 nature 467 nature 505 nature eng eong ooi & october pair-wise rna interactions 2-methylnicotinic acid imidazolide finding pair-wise interactions senior clinician-scientist award mutated long-range interactions medium high-glucose media pair-wise interaction mapping28 performed structure libraries pair-wise interaction mapping thermo fisher scientific pair-wise interactions fold nearest long-range interaction pair-wise interactions resulted rescue pair-wise interactions shared pair-wise interactions wilcoxon rank-sum test shorter-range interactions tend conserved long-range interaction altered rna–protein interactions disrupt pair-wise interactions virion pair-wise interactions science—branco weiss fellowship incorporating nai-map reactivities longer-range interactions tend partition function files interactome data correlate eng eong ooi nai-map mutation rates

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         headline:Structure mapping of dengue and Zika viruses reveals functional long-range interactions
         description:Dengue (DENV) and Zika (ZIKV) viruses are clinically important members of the Flaviviridae family with an 11 kb positive strand RNA genome that folds to enable virus function. Here, we perform structure and interaction mapping on four DENV and ZIKV strains inside virions and in infected cells. Comparative analysis of SHAPE reactivities across serotypes nominates potentially functional regions that are highly structured, conserved, and contain low synonymous mutation rates. Interaction mapping by SPLASH identifies many pair-wise interactions, 40% of which form alternative structures, suggesting extensive structural heterogeneity. Analysis of shared interactions between serotypes reveals a conserved macro-organization whereby interactions can be preserved at physical locations beyond sequence identities. We further observe that longer-range interactions are preferentially disrupted inside cells, and show the importance of new interactions in virus fitness. These findings deepen our understanding of Flavivirus genome organization and serve as a resource for designing therapeutics in targeting RNA viruses. Here, the authors provide detailed analyses of viral RNA structure in virions and in infected cells for four dengue virus serotypes and four Zika virus strains, and identify conserved structures that are important for virus replication.
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            RNA folding
            Viral infection
            Science
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      headline:Structure mapping of dengue and Zika viruses reveals functional long-range interactions
      description:Dengue (DENV) and Zika (ZIKV) viruses are clinically important members of the Flaviviridae family with an 11 kb positive strand RNA genome that folds to enable virus function. Here, we perform structure and interaction mapping on four DENV and ZIKV strains inside virions and in infected cells. Comparative analysis of SHAPE reactivities across serotypes nominates potentially functional regions that are highly structured, conserved, and contain low synonymous mutation rates. Interaction mapping by SPLASH identifies many pair-wise interactions, 40% of which form alternative structures, suggesting extensive structural heterogeneity. Analysis of shared interactions between serotypes reveals a conserved macro-organization whereby interactions can be preserved at physical locations beyond sequence identities. We further observe that longer-range interactions are preferentially disrupted inside cells, and show the importance of new interactions in virus fitness. These findings deepen our understanding of Flavivirus genome organization and serve as a resource for designing therapeutics in targeting RNA viruses. Here, the authors provide detailed analyses of viral RNA structure in virions and in infected cells for four dengue virus serotypes and four Zika virus strains, and identify conserved structures that are important for virus replication.
      datePublished:2019-03-29T00:00:00Z
      dateModified:2019-03-29T00:00:00Z
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         Dengue virus
         RNA folding
         Viral infection
         Science
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         multidisciplinary
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