G2-quadruplex in the 3’UTR of IE180 regulates Pseudorabies virus replication by enhancing gene expression
G2-quadruplex in the 3’UTR of IE180 regulates Pseudorabies virus replication by enhancing gene expression
复制标题
IE180 3-UTR 中的 G2 四链体通过增强基因表达来调节伪狂犬病病毒复制
DOI：
10.1080/15476286.2020.1731664
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发表时间：
2020-02
期刊：
影响因子：
4.1
通讯作者：
Dengguo Wei
中科院分区：
文献类型：
--
作者：
Ya-Shu Zhang;Si-Si Liu;Hui Jiang;Hui Deng;Chen Dong;Wei Shen;Hai-Feng Chen;Chao Gao;Shao-Bo Xiao;Zheng-Fei Liu;Dengguo Wei
摘要mRNA 3 ′非翻译区（3 ′ UTR）中的RNA二级结构元件在转录后调控中起重要作用。病毒RNA中的RNA结构元件为研究多种调控机制提供了有价值的模型。疱疹病毒基因组是具有富含GC序列的双链DNA，其可以转录成丰富的富含GC的RNA。研究这些富含GC的RNA的结构和功能具有重要意义。在伪狂犬病病毒（Pseudorabies virus，PRV）即早基因3 ′端非翻译区（3 ′ UTR）中发现了一段G2-四链体形成序列PQS 18 -1。RNA PQS 18 -1折叠成平行的G-四链体结构，增强基因表达。非G-四链体突变体和G3-四链体突变体在3个非翻译区的基因表达水平均低于野生型G2-四链体。TMPyP 4破坏PQS 18 -1 G2-四链体并抑制基因表达，从而在感染后24小时将PK 15细胞中的PRV复制降低一个滴度。结果表明，IE 180基因3 ′ UTR的RNA G2-quadruplex是其高表达所必需的，它可能是一个特异性的转录后调控元件，对小分子或其他大分子物质起反应。本研究在α疱疹病毒立即早期基因的3 ′ UTR中发现了一个新的RNA G2-四链体，为抗病毒药物设计提供了新的核酸靶点。图形摘要
ABSTRACT RNA secondary structure elements in the mRNA 3ʹ-untranslated regions (3ʹUTR) play important roles in post-transcriptional regulation. RNA structure elements in the viral RNA provide valuable model for studying diverse regulation mechanisms. Herpesvirus genomes are double-stranded DNA with GC-rich sequences, which can be transcribed into abundant GC-rich RNAs. It is valuable to explore the structures and function of those GC-rich RNAs. We identified a G2-quadruplex-forming sequence named PQS18-1 in the 3ʹUTR of the unique immediate early gene of Pseudorabies virus (PRV), an important member of Alphaherpesvirinae subfamily. The RNA PQS18-1 was folded into parallel G-quadruplex structure, enhancing gene expression. Both non-G-quadruplex mutant and G3-quadruplex mutant in the 3ʹUTR showed lower gene expression level than the wildtype G2-quadruplex. TMPyP4 destroyed PQS18-1 G2-quadruplex and suppressed gene expression, accordingly reducing PRV replication by one titre in the PK15 cells at 24 h post infection. Our findings indicated that the RNA G2-quadruplex in 3ʹUTR was essential for high expression of IE180 gene, and it could be a specific post-transcription regulation element in response to small molecules or other macromolecules. This study discovers a novel RNA G2-quadruplex in the 3ʹUTR of an immediate early gene of alphaherpesvirus and provides a new nucleic acid target for anti-virus drug design. Graphical abstract
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影响因子：
14.9
作者：
Mergny JL;Li J;Lacroix L;Amrane S;Chaires JB
通讯作者：
Chaires JB
G(2)-四链体控制多胺生物合成途径。
影响因子：
7.7
作者：
Lightfoot HL;Hagen T;Cléry A;Allain FH;Hall J
通讯作者：
Hall J
影响因子：
64.8
作者：
Chen MC;Tippana R;Demeshkina NA;Murat P;Balasubramanian S;Myong S;Ferré-D'Amaré AR
通讯作者：
Ferré-D'Amaré AR
影响因子：
16.6
作者：
Hartwick EW;Costantino DA;MacFadden A;Nix JC;Tian S;Das R;Kieft JS
通讯作者：
Kieft JS
影响因子：
15
作者：
Dai, Jixun;Carver, Megan;Hurley, Laurence H.;Yang, Danzhou
通讯作者：
Yang, Danzhou