miR-K12-7-5p encoded by Kaposi's sarcoma-associated herpesvirus stabilizes the latent state by targeting viral ORF50/RTA.
miR-K12-7-5p encoded by Kaposi's sarcoma-associated herpesvirus stabilizes the latent state by targeting viral ORF50/RTA.
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卡波西肉瘤相关疱疹病毒编码的 miR-K12-7-5p 通过靶向病毒 ORF50/RTA 稳定潜伏状态
DOI：
10.1371/journal.pone.0016224
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发表时间：
2011-01-20
期刊：
影响因子：
3.7
通讯作者：
Lan K
中科院分区：
文献类型：
--
作者：
Lin X;Liang D;He Z;Deng Q;Robertson ES;Lan K
目前已鉴定出17个由Kaposi肉瘤相关疱疹病毒(KSHV)编码的miRNAs，并对其功能进行了初步研究。在这些miRNAs中，我们报道了miR-K12-7直接靶向由开放阅读框架50编码的复制和转录激活因子(RTA)。我们发现miR-K12-7以种子序列依赖的方式靶向RTA 3‘非翻译区(RTA3’UTR)。来自miR-K12-7的miR-K12-7-5p介导了RTA表达的抑制，种子匹配位点的突变完全消除了miR-K12-7对RTA3‘UTR的抑制作用。在潜伏感染KSHV的293/Bac36细胞中，分别瞬时转染miR-K12-7表达载体和miR-K12-7-5p特异性抑制剂，进一步证实miR-K12-7对RTA表达的抑制作用。将miR-K12-7瞬时导入293/Bac36细胞，可降低RTA的表达及RTA调控的下游早期基因的表达，经化学诱导剂处理后，子代病毒的产量明显减少。我们的研究发现，另一种miRNA miR-K12-7-5p针对病毒即刻早期基因RTA，该miRNA有助于维持病毒潜伏期。
Seventeen miRNAs encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) have been identified and their functions have begun to be characterized. Among these miRNAs, we report here that miR-K12-7 directly targets the replication and transcription activator (RTA) encoded by open reading frame 50. We found that miR-K12-7 targeted the RTA 3′ untranslated region (RTA3′UTR) in a seed sequence-dependent manner. miR-K12-7-5p derived from miR-K12-7 mediates the inhibition of RTA expression, and the mutation of the seed match site totally abrogated the inhibitory effect of miR-K12-7 on RTA3′UTR. The inhibition of RTA expression by miR-K12-7 was further confirmed in the latently KSHV-infected 293/Bac36 cell line through transient transfection of miR-K12-7 expression plasmid or specific inhibitor of miR-K12-7-5p, respectively. The transient transfection of miR-K12-7 into 293/Bac36 cells reduced RTA expression and the expression of the downstream early genes regulated by RTA, and also the production of progeny virus was significantly reduced after treatment with chemical inducers. Our study revealed that another miRNA, miR-K12-7-5p, targets the viral immediate early gene RTA and that this miRNA contributes to the maintenance of viral latency.
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影响因子：
5.4
作者：
Umbach, Jennifer L.;Cullen, Bryan R.
通讯作者：
Cullen, Bryan R.
影响因子：
5.4
作者：
Izumiya, Yoshihiro;Izumiya, Chie;Kung, Hsing-Jien
通讯作者：
Kung, Hsing-Jien
影响因子：
4.5
作者：
Grundhoff, A;Sullivan, CS;Ganem, D
通讯作者：
Ganem, D
DOI：
10.1073/pnas.0711910105
发表时间：
2008-04-08
影响因子：
11.1
作者：
Murphy, Eain;Vanicek, Jiri;Levine, Arnold J.
通讯作者：
Levine, Arnold J.
影响因子：
5.4
作者：
Song, MJ;Brown, HJ;Sun, R
通讯作者：
Sun, R