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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
Synthetic translational regulation by an L7Ae-kink-turn RNP switch
Hirohide Saito1, Tetsuhiro Kobayashi, Tomoaki Hara
1Laboratory of Gene Biodynamics, Graduate School of Biostudies, Kyoto University, Oiwake-cho, Kitashirakawa, Sakyo-ku, Kyoto, Japan. h-saito@kuchem.kyoto-u.ac.jp
Abstract:
The regulation of cell signaling pathways and the reconstruction of genetic circuits are important aspects of bioengineering research. Both of these goals require molecular devices to transmit information from an input biomacromolecule to the desired outputs. Here, we show that an RNA-protein (RNP)-containing L7Ae-kink-turn interaction can be used to construct translational regulators under control of an input protein that regulates the expression of desired output proteins. We built a system in which L7Ae, an archaeal ribosomal protein, regulates the translation of a designed mRNA in vitro and in human cells. The translational regulator composed of the RNP might provide new therapeutic strategies based on the detection, repair or rewiring of intrinsic cellular defects, and it may also serve as an invaluable tool for the dissection of the behavior of complex, higher-order circuits in the cell.
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