A structured RNA in hepatitis B virus post-transcriptional regulatory element represses alternative splicing in a sequence-independent and position-dependent manner.
A structured RNA in hepatitis B virus post-transcriptional regulatory element represses alternative splicing in a sequence-independent and position-dependent manner.
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DOI：
10.1111/j.1742-4658.2011.08077.x
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发表时间：
2011-05
期刊：
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Huang C;Xie MH;Liu W;Yang B;Yang F;Huang J;Huang J;Wu Q;Fu XD;Zhang Y
乙型肝炎病毒（HBV）转录物受到多个剪接决定，但剪接调节机制仍然知之甚少。在这项研究中，我们使用了一个经过充分研究的剪接报告基因来解剖HBV转录后调控元件（PRE）中的剪接调控元件。研究人员发现了一种强内含子剪接沉默子（ISS），其最小功能元件为105个核苷酸（简称PREISS）。有趣的是，该元件的正义链和反义链在多种人类细胞系中都能强烈抑制选择性剪接。PRE-ISS折叠成双发夹结构，其中破坏双发夹结构的取代突变取消了剪接沉默子的活性。虽然PRE-ISS含有两个先前鉴定的多聚嘧啶束结合蛋白的结合位点，但它能独立于该蛋白抑制剪接。PRE-ISS的沉默功能表现出强烈的位置依赖性，随着距离受影响剪接位点的距离而降低。到目前为止，PRE-ISS不属于任何HBV剪接变异的内含子区，这阻碍了对这种内含子沉默功能在HBV剪接调节中的测试。这些发现，再加上HBV基因组中多个义-反义ISSs的鉴定，支持了一种序列独立和结构依赖的调节机制可能已经进化到抑制HBV转录物中的隐剪接位点，从而防止它们在宿主病毒复制过程中的异常剪接的假设。
Hepatitis B virus (HBV) transcripts are subjected to multiple splicing decisions, but the mechanism of splicing regulation remains poorly understood. In this study, we used a well-investigated alternative splicing reporter to dissect splicing regulatory elements residing in the post-transcriptional regulatory element (PRE) of HBV. A strong intronic splicing silencer (ISS) with a minimal functional element of 105 nucleotides (referred to as PREISS) was identified and, interestingly, both the sense and antisense strands of the element were found to strongly suppress alternative splicing in multiple human cell lines. PRE-ISS folds into a double-hairpin structure, in which substitution mutations disrupting the double-hairpin structure abolish the splicing silencer activity. Although it harbors two previously identified binding sites for polypyrimidine tract binding protein, PRE-ISS represses splicing independent of this protein. The silencing function of PRE-ISS exhibited a strong position dependence, decreasing with the distance from affected splice sites. PRE-ISS does not belong to the intronic region of any HBV splicing variants identified thus far, preventing the testing of this intronic silencer function in the regulation of HBV splicing. These findings, together with the identification of multiple sense–antisense ISSs in the HBV genome, support the hypothesis that a sequence-independent and structure-dependent regulatory mechanism may have evolved to repress cryptic splice sites in HBV transcripts, thereby preventing their aberrant splicing during viral replication in the host.
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影响因子：
5.3
作者：
Gladman JT;Chandler DS
通讯作者：
Chandler DS
DOI：
10.1073/pnas.0700343104
发表时间：
2007-02-27
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
5.3
作者：
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通讯作者：
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影响因子：
4.8
作者：
Muh, SJ;Hovhannisyan, RH;Carstens, RP
通讯作者：
Carstens, RP
影响因子：
3.9
作者：
Sawicka, Kirsty;Bushell, Martin;Willis, Anne E.
通讯作者：
Willis, Anne E.