Three-dimensional structure of a flavivirus dumbbell RNA reveals molecular details of an RNA regulator of replication.

Three-dimensional structure of a flavivirus dumbbell RNA reveals molecular details of an RNA regulator of replication.
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DOI:
10.1093/nar/gkab462
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发表时间:
2021-07-09
影响因子:
14.9
通讯作者:
Kieft JS
Kieft JS
中科院分区:
生物学2区
文献类型:
--
作者:
Akiyama BM;Graham ME;O Donoghue Z;Beckham JD;Kieft JS

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蚊媒黄病毒(MBFV)包括登革热、西尼罗河病毒、黄热病和寨卡病毒,其RNA基因组编码一个开放阅读框,两侧有5‘和3’非翻译区(UTRs)。MBFV的3‘UTRs在被称为哑铃(Db)的结构化RNA元件中包含高序列保守区。DBS调节病毒RNA基因组的翻译和复制,其功能被认为依赖于RNA假结的形成。为了了解DB Structure是如何提供这一功能的,我们将东港病毒DB的X射线晶体结构解析为2.1?分辨率,并使用结构建模来揭示其三维折叠的细节。结构证实了预测的假结,分子模拟揭示了保守序列是如何形成四向连接的,似乎稳定了假结。单分子FRET表明,DB伪结是一个稳定的元件,可以通过调节长程RNA构象变化来调节病毒生命周期中翻译和复制之间的切换。
Mosquito-borne flaviviruses (MBFVs) including dengue, West Nile, yellow fever, and Zika viruses have an RNA genome encoding one open reading frame flanked by 5′ and 3′ untranslated regions (UTRs). The 3′ UTRs of MBFVs contain regions of high sequence conservation in structured RNA elements known as dumbbells (DBs). DBs regulate translation and replication of the viral RNA genome, functions proposed to depend on the formation of an RNA pseudoknot. To understand how DB structure provides this function, we solved the x-ray crystal structure of the Donggang virus DB to 2.1Å resolution and used structural modeling to reveal the details of its three-dimensional fold. The structure confirmed the predicted pseudoknot and molecular modeling revealed how conserved sequences form a four-way junction that appears to stabilize the pseudoknot. Single-molecule FRET suggests that the DB pseudoknot is a stable element that can regulate the switch between translation and replication during the viral lifecycle by modulating long-range RNA conformational changes.
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