Promoter-associated small double-stranded RNA interacts with heterogeneous nuclear ribonucleoprotein A2/B1 to induce transcriptional activation
Promoter-associated small double-stranded RNA interacts with heterogeneous nuclear ribonucleoprotein A2/B1 to induce transcriptional activation
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DOI：
10.1042/bj20120256
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发表时间：
2012-11-01
影响因子：
4.1
通讯作者：
Ye, Zhang-Qun
中科院分区：
文献类型：
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作者：
Hu, Jia;Chen, Zhong;Ye, Zhang-Qun
最近的一些报道表明，与启动子区域互补的小激活dsRNA[双链RNA；Sarna(小激活dsRNA)]可以上调哺乳动物细胞中基因的表达，这种现象被称为RNAa(RNA激活)。然而，对于启动子靶向的SARNA的靶分子是什么以及参与这一过程的蛋白质来说，RNAa的机制仍然不清楚。P21(Waf1/CIP)(P21)[CDKN1A(细胞周期蛋白依赖性激酶抑制因子1A)]是一种重要的肿瘤抑制基因，是RNAa在肿瘤细胞中激活的基因之一。在本研究中，我们提供了p21启动子靶向的Sarna与其在p21启动子上的预定靶点相互作用以激活p21表达的直接证据。这一过程与RNA聚合酶II和AGO2(ArgAerte2)蛋白在SARNA靶点的募集有关。此外，我们还发现了几个hnRNPs(异质性核糖核蛋白)(A1、A2/B1和C1/C2)与Sarna相关。进一步的研究表明，hnRNPA2/B1在体内和体外与Sarna相互作用，是RNAa活性所必需的。这些发现表明，RNAa是针对启动子的特定靶向的结果，并揭示了RNAa的额外机制细节。
Several recent reports have demonstrated that small activating dsRNA [double-stranded RNA; saRNA (small activating dsRNA)] complementary to promoter regions can up-regulate gene expression in mammalian cells, a phenomenon termed RNAa (RNA activation). However, the mechanism of RNAa remains obscure with regard to what is the target molecule for promoter-targeted saRNA and what are the proteins involved in this process. p21(Waf1/CiP]) (p21) [CDKN1A (cyclin-dependent kinase inhibitor 1A)], an important tumour suppressor gene, is among the genes that can be activated by RNAa in tumour cells. In the present study, we provide direct evidence that p21 promoter-targeted saRNA interact with its intended target on the p21 promoter to activate p21 expression. This process is associated with recruitment of RNA polymerase II and AGO2 (argonaute 2) protein to the saRNA-target site. Additionally, we found that several hnRNPs (heterogeneous nuclear ribonucleoproteins) (A1, A2/B1 and C1/C2) are associated with saRNA. Further studies show that hnRNPA2/B1 interacts with the saRNA in vivo and in vitro and is required for RNAa activity. These findings indicate that RNAa results from specific targeting of promoters and reveals additional mechanistic details of RNAa.