Sendai virus trailer RNA binds TIAR, a cellular protein involved in virus-induced apoptosis
Sendai virus trailer RNA binds TIAR, a cellular protein involved in virus-induced apoptosis
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DOI：
10.1093/emboj/cdf513
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发表时间：
2002-10-01
期刊：
影响因子：
11.4
通讯作者：
Kolakofsky, D
中科院分区：
文献类型：
--
作者：
Iseni, F;Garcin, D;Kolakofsky, D
仙台病毒（SeV）前导（le）和尾随（tr）RNA分别是在失败的反基因组和基因组合成期间产生的短转录物。表达来自前导区的tr样RNA的重组SeV（rSeV）是非致细胞病变的，并且此外，防止野生型SeV在混合感染中诱导细胞凋亡。因此，这些rSeV似乎获得了功能。在这里，我们报告了TR RNA通过富含AU的序列5' UUUUAAAUUUU与细胞凋亡（TIAR）有许多联系的细胞蛋白结合。这种富含AU的序列在Ie RNA内的单独复制赋予TIAR在这种Ie * RNA上的结合和细胞培养物中这些rSeV的非细胞病变表型。在SeV感染期间TIAR的转基因过表达促进细胞凋亡并逆转le* RNA表达的抗细胞凋亡作用。此外，TIAR过表达和SeV感染协同作用以诱导细胞凋亡。这些短的病毒RNA可能通过隔离TIAR起作用，TIAR是一种参与SeV诱导的细胞凋亡的多价RNA识别基序（RRM）家族RNA结合蛋白。在这种观点中，TR RNA不仅仅是失败的基因组合成的副产物，而且还是调节细胞抗病毒反应的反基因组转录物。
Sendai virus (SeV) leader (le) and trailer (tr) RNAs are short transcripts generated during abortive antigenome and genome synthesis, respectively. Recombinant SeV (rSeV) that express tr-like RNAs from the leader region are non-cytopathic and, moreover, prevent wild-type SeV from inducing apoptosis in mixed infections. These rSeV thus appear to have gained a function. Here we report that tr RNA binds to a cellular protein with many links to apoptosis (TIAR) via the AU-rich sequence 5' UUUUAAAUUUU. Duplication of this AU-rich sequence alone within the le RNA confers TIAR binding on this le* RNA and a non-cytopathic phenotype to these rSeV in cell culture. Transgenic overexpression of TIAR during SeV infection promotes apoptosis and reverses the anti-apoptotic effects of le* RNA expression. Moreover, TIAR overexpression and SeV infection act synergistically to induce apoptosis. These short viral RNAs may act by sequestering TIAR, a multivalent RNA recognition motif (RRM) family RNA-binding protein involved in SeV-induced apoptosis. In this view, tr RNA is not simply a by-product of abortive genome synthesis, but is also an antigenome transcript that modulates the cellular antiviral response.