Predictive design of mRNA translation initiation region to control prokaryotic translation efficiency |
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| Institution: | 1. Department of Chemical Engineering, Pohang University of Science and Technology, San 31, Hyoja-dong, Nam-gu, Pohang, Gyeongbuk 790-784, South Korea;2. School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, San 31, Hyoja-dong, Nam-gu, Pohang, Gyeongbuk 790-784, South Korea;3. Division of Molecular and Life Science, Pohang University of Science and Technology, San 31, Hyoja-dong, Nam-gu, Pohang, Gyeongbuk 790-784, South Korea;4. Division of IT Convergence Engineering, Pohang University of Science and Technology, San 31, Hyoja-dong, Nam-gu, Pohang, Gyeongbuk 790-784, South Korea;1. Department of Life Sciences, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, Korea;2. Department of Chemical Engineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, Korea;3. School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, Korea;4. Department of Chemical and Biological Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea;1. Department of Chemical Engineering and Pohang University of Science and Technology, 77 Cheongam-Ro, Nam-Gu, Pohang, Gyeongbuk 37673, Republic of Korea;2. School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, 77 Cheongam-Ro, Nam-Gu, Pohang, Gyeongbuk 37673, Republic of Korea;3. School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology, 50, UNIST-gil, Ulsan 44919, Republic of Korea;4. School of Chemical and Biological Engineering, Institute of Chemical Process, Seoul National University, 1 Gwanak-Ro, Gwanak-Gu, Seoul 08826, Republic of Korea;1. Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), 34141 Daejeon, Republic of Korea;2. Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, KAIST, Daejeon 34141, Republic of Korea;3. BioProcess Engineering Research Center and BioInformatics Research Center, KAIST, 34141 Daejeon, Republic of Korea;4. School of Integrative Engineering, Chung-Ang University, 06974 Seoul, Republic of Korea;1. School of Energy and Chemical Engineering, UNIST, 50, Ulsan 44919, Republic of Korea;2. Department of Biology and Bioengineering, Division of Industrial Biotechnology, Chalmers University of Technology, kemivagen 10, 412 96 Goteborg, Sweden;3. Department of Biotechnology, Vel Tech Rangarajan Dr. Sagunthala R&D Institute of Science and Technology, Avadi, Chennai 600062, India;1. Department of Chemical Engineering, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, 30013 Hsinchu, Taiwan;2. Material and Chemical Research Laboratories, Industrial Technology Research Institute, 101, Section 2, Kuang-Fu Road, 30013 Hsinchu, Taiwan |
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| Abstract: | Precise prediction of prokaryotic translation efficiency can provide valuable information for optimizing bacterial host for the production of biochemical compounds or recombinant proteins. However, dynamic changes in mRNA folding throughout translation make it difficult to assess translation efficiency. Here, we systematically determined the universal folding regions that significantly affect the efficiency of translation in Escherichia coli. By assessing the specific regions for mRNA folding, we could construct a predictive design method, UTR Designer, and demonstrate that proper codon optimization around the 5′-proximal coding sequence is necessary to achieve a broad range of expression levels. Finally, we applied our method to control the threshold value of input signals switching on a genetic circuit. This should increase our understanding of the processes underlying gene expression and provide an efficient design principle for optimizing various biological systems, thereby facilitating future efforts in metabolic engineering and synthetic biology. |
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