RBM24 stabilizes hepatitis B virus pregenomic RNA but inhibits core protein translation by targeting the terminal redundancy sequence.
RBM24 stabilizes hepatitis B virus pregenomic RNA but inhibits core protein translation by targeting the terminal redundancy sequence.
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DOI：
10.1038/s41426-018-0091-4
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发表时间：
2018-05-14
影响因子：
13.2
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Yao Y;Yang B;Cao H;Zhao K;Yuan Y;Chen Y;Zhang Z;Wang Y;Pei R;Chen J;Hu X;Zhou Y;Lu M;Wu C;Chen X
3.5kb的乙肝病毒(HBVRNA)RNA的末端冗余(TR)序列包含控制病毒生命周期中许多关键功能的位点，包括多聚腺苷化、翻译、RNA包装和DNA合成。在本研究中，RNA结合基序蛋白24(RBM24)被证明通过靶向HBVRNA的TR而参与调控HBVRNA的复制。在乙肝病毒感染的肝癌细胞系中，RBM24基因的敲除和过表达都导致了乙肝病毒复制和转录的降低。异位表达的RBM24抑制了乙肝病毒的复制，而通过敲除RBM24可以部分恢复这种抑制作用，这表明适当水平的RBM24是乙肝病毒复制所必需的。RBM24对乙肝病毒复制和翻译的调控是通过RBM24的RNA结合域与3.5kb RNA的5‘和3’TR区相互作用实现的。RBM24与HBV前基因组RNA(PgRNA)的5‘TR区相互作用，阻断HBVpgRNA上的80S核糖体组装，从而抑制核心蛋白的翻译，而RBM24与3’TR区的相互作用增强了HBVRNA的稳定性。最后，在一个乙肝病毒感染模型中进一步证实了RBM24对乙肝病毒复制的调控作用。综上所述，本研究通过与病毒RNA的不同转录因子相互作用证明了RBM24的双重功能，并揭示了RBM24是一个重要的病毒复制宿主基因。
The terminal redundancy (TR) sequence of the 3.5-kb hepatitis B virus (HBV) RNA contains sites that govern many crucial functions in the viral life cycle, including polyadenylation, translation, RNA packaging, and DNA synthesis. In the present study, RNA-binding motif protein 24 (RBM24) is shown to be involved in the modulation of HBV replication by targeting the TR of HBV RNA. In HBV-transfected hepatoma cell lines, both knockdown and overexpression of RBM24 led to decreased HBV replication and transcription. Ectopic expression of RBM24 inhibited HBV replication, which was partly restored by knockdown of RBM24, indicating that a proper level of RBM24 was required for HBV replication. The regulation of RBM24 of HBV replication and translation was achieved by the interaction between the RNA-binding domains of RBM24 and both the 5′ and 3′ TR of 3.5-kb RNA. RBM24 interacted with the 5′ TR of HBV pregenomic RNA (pgRNA) to block 80S ribosome assembly on HBV pgRNA and thus inhibited core protein translation, whereas the interaction between RBM24 and the 3′ TR enhanced the stability of HBV RNA. Finally, the regulatory function of RBM24 on HBV replication was further confirmed in a HBV infection model. In conclusion, the present study demonstrates the dual functions of RBM24 by interacting with different TRs of viral RNA and reveals that RBM24 is an important host gene for HBV replication.
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影响因子：
5
作者：
Assogba, BD;Choi, BH;Rho, HM
通讯作者：
Rho, HM
影响因子：
4.9
作者：
Ladner, SK;Otto, MJ;King, RW
通讯作者：
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影响因子：
4.4
作者：
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通讯作者：
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影响因子：
14.9
作者：
Barreau C;Paillard L;Osborne HB
通讯作者：
Osborne HB
宿主锌指抗病毒蛋白抑制乙型肝炎病毒复制
影响因子：
6.7
作者：
Mao R;Nie H;Cai D;Zhang J;Liu H;Yan R;Cuconati A;Block TM;Guo JT;Guo H
通讯作者：
Guo H