Critical role of hnRNP A1 in HTLV-1 replication in human transformed T lymphocytes.
Critical role of hnRNP A1 in HTLV-1 replication in human transformed T lymphocytes.
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DOI：
10.1186/1742-4690-2-8
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发表时间：
2005-02-09
期刊：
影响因子：
3.3
通讯作者：
Duc Dodon M
中科院分区：
文献类型：
--
作者：
Kress E;Baydoun HH;Bex F;Gazzolo L;Duc Dodon M
在这项研究中，我们已经研究了异质核核糖核蛋白A1（hnRNPA 1）的作用，在病毒基因表达的T淋巴细胞转化HTLV-1。我们先前已经观察到hnRNPA 1（A1）下调HTLV-1的雷克斯蛋白的转录后活性。在这里，我们测试了是否异位表达的显性负突变体（NLS-A1-HA）的穿梭活动或敲低的hnRNPA 1基因缺陷，使用RNA干扰可以抑制Rex介导的输出的病毒mRNA的HTLV-1生产C91 PL T细胞。我们表明，NLS-A1-HA的表达不修改Rex依赖性病毒mRNA的输出。相反，通过RNA干扰抑制C91 PL细胞中A1的表达引起未剪接和单剪接mRNA的Rex依赖性输出增加。令人惊讶的是，我们还观察到前病毒转录的显著增加和未剪接mRNA的积累，表明剪接过程受到影响。最后，C91 PL细胞中A1的敲除增加了这些细胞的病毒产量。因此，hnRNP A1与由该人逆转录病毒转化的T细胞中HTLV-1基因表达水平的调节有关。这些观察结果提供了一个新的细胞控制HTLV-1复制的见解，并建议hnRNP A1可能是这种人类逆转录病毒在T细胞中的生命周期的调节机制的一部分。
In this study, we have examined the role of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) in viral gene expression in T lymphocytes transformed by HTLV-1. We have previously observed that hnRNP A1 (A1) down-modulates the post transcriptional activity of Rex protein of HTLV-1. Here, we tested whether the ectopic expression of a dominant negative mutant (NLS-A1-HA) defective in shuttling activity or knockdown of the hnRNPA1 gene using RNA interference could inhibit Rex-mediated export of viral mRNAs in HTLV-1 producing C91PL T-cells. We show that the expression of NLS-A1-HA does not modify the export of Rex-dependent viral mRNAs. Conversely, inhibiting A1 expression in C91PL cells by RNA interference provoked an increase in the Rex-dependent export of unspliced and singly spliced mRNAs. Surprisingly, we also observed a significant increase in proviral transcription and an accumulation of unspliced mRNAs, suggesting that the splicing process was affected. Finally, A1 knockdown in C91PL cells increased viral production by these cells. Thus, hnRNP A1 is implicated in the modulation of the level of HTLV-1 gene expression in T cells transformed by this human retrovirus. These observations provide an insight into a new cellular control of HTLV-1 replication and suggest that hnRNP A1 is likely part of the regulatory mechanisms of the life cycle of this human retrovirus in T cells.
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DOI：
10.1073/pnas.77.12.7415
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
POIESZ, BJ;RUSCETTI, FW;GALLO, RC
通讯作者：
GALLO, RC
影响因子：
5.3
作者：
Iervolino, A;Santilli, G;Perrotti, D
通讯作者：
Perrotti, D
影响因子：
5.4
作者：
GRASSMANN, R;BERCHTOLD, S;FLECKENSTEIN, B
通讯作者：
FLECKENSTEIN, B
影响因子：
7.8
作者：
Siomi, MC;Eder, PS;Kataoka, N;Wan, LL;Liu, Q;Dreyfuss, G
通讯作者：
Dreyfuss, G
影响因子：
5.4
作者：
HOPE, TJ;BOND, BL;PARSLOW, TG
通讯作者：
PARSLOW, TG