Dynamic network approach for the modelling of genomic sub-complexes in multi-segmented viruses.
Dynamic network approach for the modelling of genomic sub-complexes in multi-segmented viruses.
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DOI：
10.1093/nar/gky881
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发表时间：
2018-12-14
影响因子：
14.9
通讯作者：
Roy P
中科院分区：
文献类型：
--
作者：
AlShaikhahmed K;Leonov G;Sung PY;Bingham RJ;Twarock R;Roy P
基因组分段的病毒，包括流感病毒、轮状病毒和蓝舌病毒(BTV)等病原体，面临着以正确的片段数量和类型包装其遗传物质的集体挑战。在这里，我们开发了一种新的网络方法来预测不同基因组片段之间的RNA-RNA相互作用。关于多片段BTV基因组中RNA复合体形成的实验数据被用来建立该技术的概念验证。特别是，我们发现片段之间的反式相互作用发生在多个特定的位置，称为片段分类信号(SAS)，这些信号分散在每个片段上。为了验证假定的反式作用网络，我们使用了各种生化和分子技术，证实了RNA网络方法的预测。突变和反向遗传学系统的结合表明，所确定的RNA-RNA相互作用位点确实负责片段分类和复杂的形成，这是基因组包装的基本标准。这为它们作为新型药物靶点的开发铺平了道路，要么是为了抑制组装，要么是为了设计包含不完整基因组片段的有缺陷的干扰颗粒。
Viruses with segmented genomes, including pathogens such as influenza virus, Rotavirus and Bluetongue virus (BTV), face the collective challenge of packaging their genetic material in terms of the correct number and types of segments. Here we develop a novel network approach to predict RNA–RNA interactions between different genomic segments. Experimental data on RNA complex formation in the multi-segmented BTV genome are used to establish proof-of-concept of this technique. In particular, we show that trans interactions between segments occur at multiple specific sites, termed segment assortment signals (SASs) that are dispersed across each segment. In order to validate the putative trans acting networks, we used various biochemical and molecular techniques which confirmed predictions of the RNA network approach. A combination of mutagenesis and reverse genetics systems revealed that the RNA–RNA interacting sites identified are indeed responsible for segment assortment and complex formation, which are essential criteria for genome packaging. This paves the way for their exploitation as novel types of drug target, either to inhibit assembly, or for designing defective interfering particles containing an incomplete set of genomic segments.
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影响因子：
6.7
作者：
Fajardo T Jr;Sung PY;Roy P
通讯作者：
Roy P
影响因子：
28.3
作者：
Patel N;White SJ;Thompson RF;Bingham R;Weiß EU;Maskell DP;Zlotnick A;Dykeman E;Tuma R;Twarock R;Ranson NA;Stockley PG
通讯作者：
Stockley PG
DOI：
10.3390/v9070167
发表时间：
2017-06-29
期刊：
Viruses
影响因子：
--
作者：
Fajardo T;Sung PY;Celma CC;Roy P
通讯作者：
Roy P
影响因子：
14.9
作者：
Ding, Y;Chan, CY;Lawrence, CE
通讯作者：
Lawrence, CE
影响因子：
5.4
作者：
Boyce, Mark;Celma, Cristina C. P.;Roy, Polly
通讯作者：
Roy, Polly