LUC7L3/CROP inhibits replication of hepatitis B virus via suppressing enhancer II/basal core promoter activity.
LUC7L3/CROP inhibits replication of hepatitis B virus via suppressing enhancer II/basal core promoter activity.
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DOI：
10.1038/srep36741
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发表时间：
2016-11-18
影响因子：
4.6
通讯作者：
Suzuki T
中科院分区：
文献类型：
--
作者：
Li Y;Ito M;Sun S;Chida T;Nakashima K;Suzuki T
B型肝炎病毒（HBV）基因组核心启动子是3.5 kb前基因组和前核心RNA转录起始及病毒复制的关键区域。虽然已经鉴定了许多可能调节病毒启动子活性的宿主细胞因子，但是病毒基因表达的分子机制，特别是转录抑制的调节机制仍然是难以捉摸的。本研究通过蛋白质组学筛选，发现LUC 7 like 3 pre-mRNA splicing factor（LUC 7 L3，也称为hLuc 7A或CROP）是HBV增强子II和基本核心启动子（ENII/BCP）的一个新的相互作用伴侣，并发现LUC 7 L3是ENII/BCP的负调控因子。LUC 7 L3的基因沉默显著增加了病毒基因和抗原的表达以及ENII/BCP和核心启动子的活性。相反，LUC 7 L3的过表达抑制了它们的活性和HBV复制。此外，LUC 7 L3可能有助于促进3.5 kb RNA的剪接，这也可能参与前基因组RNA水平的负调控。这是第一次证明LUC 7 L3参与基因转录和病毒复制的调节。
The core promoter of hepatitis B virus (HBV) genome is a critical region for transcriptional initiation of 3.5 kb, pregenome and precore RNAs and for the viral replication. Although a number of host-cell factors that potentially regulate the viral promoter activities have been identified, the molecular mechanisms of the viral gene expression, in particular, regulatory mechanisms of the transcriptional repression remain elusive. In this study, we identified LUC7 like 3 pre-mRNA splicing factor (LUC7L3, also known as hLuc7A or CROP) as a novel interacting partner of HBV enhancer II and basal core promoter (ENII/BCP), key elements within the core promoter, through the proteomic screening and found that LUC7L3 functions as a negative regulator of ENII/BCP. Gene silencing of LUC7L3 significantly increased expression of the viral genes and antigens as well as the activities of ENII/BCP and core promoter. In contrast, overexpression of LUC7L3 inhibited their activities and HBV replication. In addition, LUC7L3 possibly contributes to promotion of the splicing of 3.5 kb RNA, which may also be involved in negative regulation of the pregenome RNA level. This is the first to demonstrate the involvement of LUC7L3 in regulation of gene transcription and in viral replication.
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影响因子：
4.8
作者：
Brooks, Yang S.;Wang, Guanghu;Ko, Lan
通讯作者：
Ko, Lan
DOI：
10.1007/978-1-62703-484-5_13
发表时间：
2013
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Cai, Dawei;Nie, Hui;Yan, Ran;Guo, Ju-Tao;Block, Timothy M;Guo, Haitao
通讯作者：
Guo, Haitao
影响因子：
12.7
作者：
Bläckberg, J;Kidd-Ljunggren, K
通讯作者：
Kidd-Ljunggren, K
影响因子：
5.4
作者：
Buckwold, VE;Xu, ZC;Ou, JH
通讯作者：
Ou, JH
影响因子：
9.3
作者：
Gao, Ge;Dudley, Samuel C., Jr.
通讯作者：
Dudley, Samuel C., Jr.