β-Catenin recognizes a specific RNA motif in the cyclooxygenase-2 mRNA 3'-UTR and interacts with HuR in colon cancer cells.
β-Catenin recognizes a specific RNA motif in the cyclooxygenase-2 mRNA 3'-UTR and interacts with HuR in colon cancer cells.
复制标题
DOI：
10.1093/nar/gks331
复制
发表时间：
2012-08
影响因子：
14.9
通讯作者：
Jeong S
中科院分区：
文献类型：
--
作者：
Kim I;Kwak H;Lee HK;Hyun S;Jeong S
RNA 结合蛋白通过动态结合和组合结合调节 RNA 代谢的多个步骤。除了在癌细胞中的细胞粘附和 Wnt 激活转录中发挥重要作用外，β-连环蛋白还可能通过与细胞中的靶 RNA 结合来调节 RNA 选择性剪接和稳定性。选择与β-连环蛋白特异性结合的RNA适体，以更具体地解决β-连环蛋白对RNA的识别。在这里，我们表征了 RNA 适体作为模型的结构特性，并鉴定了 β-连环蛋白 RNA 基序。在细胞 RNA、环氧合酶-2 (COX-2) mRNA 3'-非翻译区 (3'-UTR) 中发现了类似的 RNA 基序。更重要的是，β-连环蛋白的 C 端结构域与 HuR 以及与 RNA 相关的犰狳重复结构域相互作用，在体外和细胞内形成 RNA-β-连环蛋白-HuR 复合物。此外，三级RNA-蛋白质复合物主要存在于结肠癌细胞的细胞质中。因此，它可能与COX-2蛋白水平和癌症进展有关。总而言之，β-连环蛋白 RNA 适体对于推导细胞 RNA 适体和鉴定结肠癌细胞中新型致癌 RNA 蛋白网络非常有价值。
RNA-binding proteins regulate multiple steps of RNA metabolism through both dynamic and combined binding. In addition to its crucial roles in cell adhesion and Wnt-activated transcription in cancer cells, β-catenin regulates RNA alternative splicing and stability possibly by binding to target RNA in cells. An RNA aptamer was selected for specific binding to β-catenin to address RNA recognition by β-catenin more specifically. Here, we characterized the structural properties of the RNA aptamer as a model and identified a β-catenin RNA motif. Similar RNA motif was found in cellular RNA, Cyclooxygenase-2 (COX-2) mRNA 3′-untranslated region (3′-UTR). More significantly, the C-terminal domain of β-catenin interacted with HuR and the Armadillo repeat domain associated with RNA to form the RNA–β-catenin–HuR complex in vitro and in cells. Furthermore, the tertiary RNA–protein complex was predominantly found in the cytoplasm of colon cancer cells; thus, it might be related to COX-2 protein level and cancer progression. Taken together, the β-catenin RNA aptamer was valuable for deducing the cellular RNA aptamer and identifying novel and oncogenic RNA–protein networks in colon cancer cells.