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首页> 外文期刊>Molecular and Cellular Biology >The Herpesvirus saimiri Small Nuclear RNAs Recruit AU-Rich Element-Binding Proteins but Do Not Alter Host AU-Rich Element-Containing mRNA Levels in Virally Transformed T Cells
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The Herpesvirus saimiri Small Nuclear RNAs Recruit AU-Rich Element-Binding Proteins but Do Not Alter Host AU-Rich Element-Containing mRNA Levels in Virally Transformed T Cells

机译:疱疹病毒saimiri小核RNA募集富含AU的元素结合蛋白,但不会改变病毒转化T细胞中含有宿主富含AU的元素的mRNA水平

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Herpesvirus saimiri (HVS) encodes seven Sm-class small nuclear RNAs, called HSURs (for Herpesvirus saimiri U RNAs), that are abundantly expressed in HVS-transformed, latently infected marmoset T cells but are of unknown function. HSURs 1, 2, and 5 have highly conserved 5′-end sequences containing the AUUUA pentamer characteristic of AU-rich elements (AREs) that regulate the stability of many host mRNAs, including those encoding most proto-oncogenes and cytokines. To test whether the ARE-containing HSURs act to sequester host proteins that regulate the decay of these mRNAs, we demonstrate their in vivo interaction with the ARE-binding proteins hnRNP D and HuR in HVS-transformed T cells using a new cross-linking assay. Comprehensive Northern and microarray analyses revealed, however, that the levels of endogenous ARE-containing mRNAs are not altered in T cells latently infected with HVS mutants lacking HSURs 1 and 2. HSUR 1 binds the destabilizing ARE-binding protein tristetraprolin induced following activation of HVS-transformed T cells, but even in such stimulated cells, the levels of host ARE-containing mRNAs are not altered by deletion of HSURs 1 and 2. Instead, HSUR 1 itself is degraded by an ARE-dependent pathway in HVS-transformed T cells, suggesting that HVS may take advantage of the host ARE-mediated mRNA decay pathway to regulate HSUR expression. This is the first example of posttranscriptional regulation of the expression of an Sm small nuclear RNA.
机译: Herpesvirus saimiri (HVS)编码7个Sm级小核RNA,称为HSURs(用于 Herpesvirus saimiri U RNA),它们在HVS转化的潜伏感染的猿猴中大量表达T细胞但功能未知。 HSUR 1、2和5具有高度保守的5'端序列,其中包含AUUUA五聚体(富含AU的元件)的特征,该元件调节许多宿主mRNA的稳定性,包括编码大多数原癌基因和细胞因子的那些mRNA。为了测试含ARE的HSUR是否能螯合调节这些mRNA衰变的宿主蛋白,我们使用新的交联实验证明了它们与ARE结合蛋白hnRNP D和HuR在HVS转化的T细胞中的体内相互作用。全面的Northern和微阵列分析表明,在潜伏感染缺乏HSURs 1和2的HVS突变体的T细胞中,内源性含ARE的mRNA的水平没有改变。HSUR1与激活HVS后诱导的去稳定化的ARE结合蛋白tristetraprolin结合。转化的T细胞,但即使在这种刺激的细胞中,包含宿主ARE的mRNA的水平也不会因HSURs 1和2的缺失而改变。相反,HSUR 1本身在HVS转化的T细胞中被ARE依赖性途径降解提示HVS可能利用宿主ARE介导的mRNA衰变途径来调节HSUR表达。这是转录后调控Sm小核RNA表达的第一个例子。

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