RTA and LANA Competitively Regulate let-7a/RBPJ Signal to Control KSHV Replication.

RTA and LANA Competitively Regulate let-7a/RBPJ Signal to Control KSHV Replication.
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RTA 和 LANA 竞争性调节 let-7a/RBPJ 信号来控制 KSHV 复制

DOI:
10.3389/fmicb.2021.804215
复制
发表时间:
2021
影响因子:
5.2
通讯作者:
Yang L
Yang L
中科院分区:
生物学2区
文献类型:
--
作者:
Di C;Zheng G;Zhang Y;Tong E;Ren Y;Hong Y;Song Y;Chen R;Tan X;Yang L

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免疫球蛋白κ J区重组信号结合蛋白(RBPJ)对卡波西肉瘤相关疱疹病毒(KSHV)复制具有双重作用。RBPJ与复制和转录激活因子(RTA)的相互作用是裂解性复制所必需的,而与潜伏相关核抗原(拉娜)的相互作用促进了潜伏感染。此外,我们前期的研究发现,拉娜通过上调miRNA let-7 a来降低RBPJ。然而,目前还不清楚RTA是否调节RBPJ的表达。在这里,我们表明RTA通过减少let-7a来增加RBPJ。在KSHV复制过程中,RBPJ表达水平与RTA表达水平呈正相关,与拉娜表达水平呈负相关。let-7a表达水平与RBPJ相反。RBPJ基因的敲除抑制了RTA启动子和拉娜启动子的自激活,减弱了拉娜对RTA启动子的抑制作用。总的来说,这些发现表明RTA和拉娜竞争let-7a/RBPJ信号以控制KSHV复制。通过RTA和拉娜调节RBPJ的表达水平在KSHV复制过程中起重要作用。
The recombination signal binding protein for immunoglobulin kappa J region (RBPJ) has a dual effect on Kaposi’s sarcoma-associated herpesvirus (KSHV) replication. RBPJ interaction with replication and transcription activator (RTA) is essential for lytic replication, while the interaction with latency-associated nuclear antigen (LANA) facilitates latent infection. Furthermore, our previous study found that LANA decreased RBPJ through upregulating miRNA let-7a. However, it is unclear whether RTA regulates the expression of RBPJ. Here, we show RTA increases RBPJ by decreasing let-7a. During KSHV replication, the RBPJ expression level was positively correlated with the RTA expression level and negatively correlated with the LANA expression level. The let-7a expression level was inverse to RBPJ. Knockdown of RBPJ inhibited the self-activation of RTA promoter and LANA promoter and weakened LANA’s inhibition of RTA promoter. Collectively, these findings indicate that RTA and LANA compete for let-7a/RBPJ signal to control the KSHV replication. Regulating the RBPJ expression level by RTA and LANA plays an important role during KSHV replication.
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