Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.
Elife. 2018 Jan 10;7:e31936. doi: 10.7554/eLife.31936.
Natural signaling circuits could be rewired to reprogram cells with pre-determined procedures. However, it is difficult to link cellular signals at will. Here, we describe signal-connectorsa series of RNA devicesthat connect one signal to another signal at the translational level. We use them to either repress or enhance the translation of target genes in response to signals. Application of these devices allows us to construct various logic gates and to incorporate feedback loops into gene networks. They have also been used to rewire a native signaling pathway and even to create novel pathways. Furthermore, logical AND gates based on these devices and integration of multiple signals have been used successfully for identification and redirection of the state of cancer cells. Eventually, the malignant phenotypes of cancers have been reversed by rewiring the oncogenic signaling from promoting to suppressing tumorigenesis. We provide a novel platform for redirecting cellular information.
天然信号通路可以通过预设程序被重新布线以重编程细胞。然而,随意连接细胞信号是很困难的。在这里,我们描述了信号连接器——一系列 RNA 器件,它们可以在翻译水平上将一个信号连接到另一个信号。我们使用它们来抑制或增强目标基因的翻译,以响应信号。这些器件的应用使我们能够构建各种逻辑门,并将反馈回路纳入基因网络。它们还被用于重新布线天然信号通路,甚至创建新的通路。此外,基于这些器件的逻辑与门以及多个信号的整合已成功用于鉴定和重定向癌细胞的状态。最终,通过将致癌信号从促进肿瘤发生重定向为抑制肿瘤发生,逆转了癌症的恶性表型。我们为重定向细胞信息提供了一个新的平台。