Exploring New Functional Aspects of HTLV-1 RNA-Binding Protein Rex: How Does Rex Control Viral Replication?
Exploring New Functional Aspects of HTLV-1 RNA-Binding Protein Rex: How Does Rex Control Viral Replication?
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DOI：
10.3390/v14020407
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发表时间：
2022-02-16
期刊：
影响因子：
--
通讯作者：
Watanabe T
中科院分区：
文献类型：
--
作者：
Nakano K;Yokoyama K;Shin S;Uchida K;Tsuji K;Tanaka M;Uchimaru K;Watanabe T
人类T细胞白血病病毒1型(HTLV-1)作为前病毒整合到人类基因组后，利用宿主T细胞基因表达机制进行病毒复制。已知的病毒RNA结合蛋白Rex可以将编码病毒结构蛋白的未剪接/不完全剪接的病毒mRNAs运出细胞核，以促进病毒颗粒的形成。然而，Rex如何避免未剪接/不完全剪接的病毒mRNAs的额外剪接并稳定它们以实现有效翻译的详细机制仍不清楚。为了阐明Rex功能的潜在分子机制，我们综合分析了Rex过表达的T细胞中基因表达和剪接模式的变化。此外，我们还鉴定了81种与Rex相互作用的人类蛋白质，这些蛋白质参与转录、剪接、翻译和mRNA质量控制。特别是，Rex与NONO和SFPQ相互作用，这两个基因在转录和剪接调控中发挥着重要作用。因此，在表达Rex的T细胞中，各种基因的表达谱和剪接模式都发生了显著的变化。尤其是缺失外显子4部分的VPD-L1mRNA，编码可溶性PD-L1，在Rex表达细胞中显著增加。总体而言，通过对这三个数据集的综合分析，我们首次表明Rex在整个途径中干预宿主基因表达机制，可能是护送病毒不稳定的mRNA从转录(START)到翻译(END)。在发挥其功能时，Rex可以改变各种基因的表达水平和剪接模式，从而影响宿主细胞的表型。
After integration to the human genome as a provirus, human T-cell leukemia virus type 1 (HTLV-1) utilizes host T cell gene expression machinery for viral replication. The viral RNA-binding protein, Rex, is known to transport unspliced/incompletely spliced viral mRNAs encoding viral structural proteins out of the nucleus to enhance virus particle formation. However, the detailed mechanism of how Rex avoids extra splicing of unspliced/incompletely spliced viral mRNAs and stabilizes them for effective translation is still unclear. To elucidate the underlying molecular mechanism of Rex function, we comprehensively analyzed the changes in gene expression and splicing patterns in Rex-overexpressing T cells. In addition, we identified 81 human proteins interacting with Rex, involved in transcription, splicing, translation, and mRNA quality control. In particular, Rex interacts with NONO and SFPQ, which play important roles in the regulation of transcription and splicing. Accordingly, expression profiles and splicing patterns of a wide variety of genes are significantly changed in Rex-expressing T cells. Especially, the level of vPD-L1 mRNA that lacks the part of exon 4, thus encodes soluble PD-L1 was significantly increased in Rex-expressing cells. Overall, by integrated analysis of these three datasets, we showed for the first time that Rex intervenes the host gene expression machinery throughout the pathway, probably to escort viral unstable mRNAs from transcription (start) to translation (end). Upon exerting its function, Rex may alter the expression level and splicing patterns of various genes, thus influencing the phenotype of the host cell.
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影响因子：
4.6
作者：
Ho TT;Huang J;Zhou N;Zhang Z;Koirala P;Zhou X;Wu F;Ding X;Mo YY
通讯作者：
Mo YY
影响因子：
6.7
作者：
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通讯作者：
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DOI：
10.1073/pnas.1601773113
发表时间：
2016-03-22
影响因子：
11.1
作者：
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通讯作者：
Steitz, Joan A.
DOI：
10.1038/nrm.2017.27
发表时间：
2017-07
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Baralle FE;Giudice J
通讯作者：
Giudice J
影响因子：
3.7
作者：
Grone, M;Koch, C;Grassmann, R
通讯作者：
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