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From RNA and Genetic Code to Life Research in the Tamura laboratory centers around investigations on the origin of life on the earth. The genetic code is the algorithm that connects RNA triplet and an amino acid through all of the biological systems, that is, archaeal, bacterial and eukaryotic systems. The origin of the genetic code has been considered in terms of “frozen accident” hypothesis by Francis Crick. However, Crick explicitly left room for stereochemical interactions between amino acids and their coding nucleotides, mentioning that “It is therefore essential to pursue the stereochemical theory…vague models of such interactions are of little use. What is wanted is direct experimental proof that these interactions take place… and some idea of their specificity.” We are focusing on the analysis of aminoacylation of tRNA by aminoacyl-tRNA synthetases (aaRSs) and its relationship to the origin of the genetic code. tRNA is the molecule that Crick predicted as an adaptor between DNA sequences and amino acids sequences. And the peptide bond formation by aminoacyl-tRNAs on the ribosome is another fundamental step in biological system. We are studying these topics through multidisciplinary approaches. Aminoacylation of RNA minihelices (primitive forms of modern tRNA) is speculated to be a key step in the transition from the putative RNA world to the theater of proteins. Here chiral preference of aminoacylation was shown with an RNA-directed aminoacylation system, suggesting the possibility that the selection of L-amino acids for proteins was determined by the stereochemistry of RNA. In addition, peptide bond formation could be achieved without the ribosome, but with a simple, minimized system that captures the essence of an interaction seen in the ribosome. In the process of elucidation of “back to life” mechanism of inactive ribozymes, we discovered that the introduction of kissing-loops revives their activity, which proved the importance of this interaction in the process of the acquisition of functions in the RNA world.
Selected Publications Ando, T. and Tamura, K. "Mechanism of chiral-selective aminoacylation of an RNA minihelix explored by QM/MM free-energy simulations" Life, 13, 722 (2023). Kawabata, M., Kawashima, K., Mutsuro-Aoki, H., Ando, T., Umehara, T. and Tamura, K. "Peptide bond formation between aminoacyl-minihelices by a scaffold derived from the peptidyl transferase center" Life, 12, 573 (2022). Arutaki, M., Kurihara, R., Matsuoka, T., Inami, A., Tokunaga, K., Ohno, T., Takahashi, H., Takano, H., Ando, T., Mutsuro-Aoki, H., Umehara, T. and Tamura, K. "G:U-independent RNA minihelix aminoacylation by Nanoarchaeum equitans alanyl-tRNA synthetase: An insight into the evolution of aminoacyl-tRNA synthetases" J. Mol. Evol., 88, 501-509 (2020). (Cover Article in JME) Tamura, K. "Perspectives on the origin of biological homochirality on Earth" J. Mol. Evol., 87, 143-146 (2019). (Cover Article in JME) Ando, T., Takahashi, S. and Tamura, K. "Principles of chemical geometry underlying chiral selectivity in RNA minihelix aminoacylation" Nucleic Acids Res., 46, 11144-11152 (2018). Tamura, K. "The genetic code: Francis Crick's legacy and beyond" Life, 6, 36 (2016). Tamura, K. "Origin of amino acid homochirality: Relationship with the RNA world and origin of tRNA aminoacylation" BioSystems, 92, 91-98 (2008). Tamura, K. and Schimmel, P. R. "Chiral-selective aminoacylation of an RNA minihelix: Mechanistic features and chiral suppression" Proc. Natl. Acad. Sci. USA, 103, 13750-13752 (2006). Tamura, K. and Schimmel, P. "Chiral-selective aminoacylation of an RNA minihelix" Science, 305, 1253 (2004). Tamura, K. and Schimmel, P. "Peptide synthesis with a template-like RNA guide and aminoacyl phosphate adaptors" Proc. Natl. Acad. Sci. USA, 100, 8666-8669 (2003). Tamura, K. and Schimmel, P. "Oligonucleotide-directed peptide synthesis in a ribosome- and ribozyme-free system" Proc. Natl. Acad. Sci. USA, 98, 1393-1397 (2001).
Related Articles Sinister amino acids or innocent victims of evolution? "Scripps Research, NEWS & VIEWS" Modern problems, primitive solutions: A glimpse into archaic protein synthesis systems "Phys.org" Bonds from the past: A journey through the history of protein synthesis "EurekAlert!" How did life begin? One key ingredient is coming into view "Nature, NEWS FEATURE" Solving the mystery of left-handed amino acids in primordial RNA reactions "Phys.org" |
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