Saito Hirohide, Fujita Yoshihiko, Kashida Shunnichi, Hayashi Karin, Inoue Tan
1] Laboratory of Gene Biodynamics, Graduate School of Biostudies, Kyoto University, Oiwake-cho, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan. [2] International Cooperative Research Project, Japan Science and Technology Agency, 5 Sanban-cho, Chiyoda-ku, Tokyo 102-0075, Japan. [3] The Hakubi Center, Kyoto University, Oiwake-cho, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan.
Nat Commun. 2011 Jan 18;2:160. doi: 10.1038/ncomms1157.
Understanding how to control cell fate is crucial in biology, medical science and engineering. In this study, we introduce a method that uses an intracellular protein as a trigger for regulating human cell fate. The ON/OFF translational switches, composed of an intracellular protein L7Ae and its binding RNA motif, regulate the expression of a desired target protein and control two distinct apoptosis pathways in target human cells. Combined use of the switches demonstrates that a specific protein can simultaneously repress and activate the translation of two different mRNAs: one protein achieves both up- and downregulation of two different proteins/pathways. A genome-encoded protein fused to L7Ae controlled apoptosis in both directions (death or survival) depending on its cellular expression. The method has potential for curing cellular defects or improving the intracellular production of useful molecules by bypassing or rewiring intrinsic signal networks.
了解如何控制细胞命运在生物学、医学和工程学中至关重要。在本研究中，我们介绍了一种利用细胞内蛋白质作为调节人类细胞命运触发因素的方法。由细胞内蛋白质L7Ae及其结合RNA基序组成的开/关翻译开关，调节所需靶蛋白的表达，并控制靶人类细胞中的两条不同凋亡途径。开关的联合使用表明，一种特定蛋白质可以同时抑制和激活两种不同mRNA的翻译：一种蛋白质实现了两种不同蛋白质/途径的上调和下调。与L7Ae融合的基因组编码蛋白质根据其细胞表达在两个方向（死亡或存活）上控制细胞凋亡。该方法有可能通过绕过或重新连接内在信号网络来治愈细胞缺陷或提高细胞内有用分子的产量。
