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
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
复制标题
DOI：
10.1128/mcb.24.10.4522-4533.2004
复制
发表时间：
2004-05-01
影响因子：
5.3
通讯作者：
Steitz, JA
中科院分区：
文献类型：
--
作者：
Cook, HL;Mischo, HE;Steitz, JA
疱疹病毒Simiri(HVS)编码7个Sm类小核RNA，称为HSURs(疱疹病毒Simiri U RNAs)，在人类疱疹病毒转化的潜伏感染的恒河猴T细胞中大量表达，但功能未知。HSUR1、2和5具有高度保守的5‘端序列，含有富AU元件(Ares)的AUUUA五聚体特征，调节许多宿主mRNAs的稳定性，包括那些编码大多数原癌基因和细胞因子的mRNAs。为了测试含ARE的HSURs是否起到隔离调节这些mRNAs衰变的宿主蛋白的作用，我们使用一种新的交联实验证明了它们在体内与HVS转化的T细胞中ARE结合蛋白hnRNP D和Hur的相互作用。然而，综合的Northern和微阵列分析显示，在潜伏感染缺乏HSURs 1和2的RVS突变体的T细胞中，内源性含有ARE的mRNAs的水平没有改变。HSUR 1结合了HSS转化的T细胞激活后诱导的不稳定的ARE结合蛋白Tristetraprolin，但即使在这样的刺激细胞中，宿主含有ARE的mRNAs的水平也不会因为HSURs 1和2的缺失而改变。相反，HSUR 1本身在HVS转化的T细胞中通过ArE依赖的途径降解，这表明HVS可能利用宿主ArE衰变的mRNA途径来调节HSUR的表达。这是第一个转录后调控Sm小核RNA表达的例子。
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 RVS 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.