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RNA 分子间和分子内相互作用调节西尼罗河病毒 3'UTR 介导的翻译调控。

Inter- and Intramolecular RNA-RNA Interactions Modulate the Regulation of Translation Mediated by the 3' UTR in West Nile Virus.

机构信息

Instituto de Parasitología y Biomedicina "López Neyra", Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), 18016 Granada, Spain.

出版信息

Int J Mol Sci. 2023 Mar 10;24(6):5337. doi: 10.3390/ijms24065337.

DOI:10.3390/ijms24065337
PMID:36982407
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10049277/
Abstract

RNA viruses rely on genomic structural elements to accomplish the functions necessary to complete the viral cycle. These elements participate in a dynamic network of RNA-RNA interactions that determine the overall folding of the RNA genome and may be responsible for the fine regulation of viral replication and translation as well as the transition between them. The genomes of members of the genus are characterized by a complexly folded 3' UTR with a number of RNA structural elements that are conserved across isolates of each species. The present work provides evidence of intra- and intermolecular RNA-RNA interactions involving RNA structural elements in the 3' UTR of the West Nile virus genome. The intermolecular interactions can be visualized in vitro by the formation of molecular dimers involving the participation of at least the SLI and 3'DB elements. Certainly, the 3' UTR of dengue virus, which lacks the SLI element, forms molecular dimers in lower quantities via a single interaction site, probably 3'DB. The functional analysis of sequence or deletion mutants revealed an inverse relationship between 3' UTR dimerization and viral translation efficiency in cell cultures. A network of RNA-RNA interactions involving 3' UTR structural elements might therefore exist, helping to regulate viral translation.

摘要

RNA 病毒依赖基因组结构元件来完成完成病毒周期所需的功能。这些元件参与 RNA-RNA 相互作用的动态网络,决定 RNA 基因组的整体折叠,并可能负责病毒复制和翻译的精细调控以及它们之间的转换。属成员的基因组的特点是 3'UTR 折叠复杂,具有许多在每个物种的分离株中保守的 RNA 结构元件。本工作提供了西尼罗河病毒基因组 3'UTR 中涉及 RNA 结构元件的分子内和分子间 RNA-RNA 相互作用的证据。通过涉及至少 SLI 和 3'DB 元件参与的分子二聚体的形成,可以在体外可视化分子间相互作用。当然,缺乏 SLI 元件的登革热病毒通过单个相互作用位点,可能是 3'DB,以较低的量形成分子二聚体。序列或缺失突变体的功能分析表明,3'UTR 二聚体化与细胞培养中的病毒翻译效率呈反比关系。因此,可能存在涉及 3'UTR 结构元件的 RNA-RNA 相互作用网络,有助于调节病毒翻译。

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