Clarification of New Control Mechanism for Correct Mapping of Genetic Information -An enzyme ensuring the correct formation of the steric structure of transfer RNA was found - (Press Release)
- Release Date
- 14 Sep, 2009
- BL41XU (Structural Biology I)
RIKEN
School of Science, The University of Tokyo
Key research achievements
• Determination of the steric structure of the complex of transfer RNA (tRNA) and the enzyme involved in the maturation of tRNA
• Discovery of mechanism behind the checking method of the completeness of the L-shaped structure of tRNA
• Expected contribution to the clarification of mechanisms of diseases associated with tRNA
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Scientists at RIKEN (Ryoji Noyori, President) and The University of Tokyo (Junichi Hamada, President) have, for the first time, clarified the control mechanism related to transfer RNA (tRNA),*1 which serves as an adapter to translate genetic codes into amino acids. By this mechanism, it is checked whether the L-shaped structure of tRNA is correctly formed to promote the accurate mapping of genetic information during the maturation of tRNA. This breakthrough was achieved by Shigeyuki Yokoyama, project director at RIKEN Systems and Structural Biology Center (also a professor of the Department of Biophysics and Biochemistry, School of Science, The University of Tokyo), Sakurako Goto-Ito, a special postdoctoral researcher of this project, and Takuhiro Ito, an assistant professor of the Department of Biophysics and Biochemistry, School of Science, The University of Tokyo. In living organisms, a cluster of molecules called tRNAs acts as an adapter during the conversion of nucleic acid sequences containing genetic information to proteins. tRNA is generated as a precursor and does not exhibit any function until it has completed a complex maturation process, which involves many enzymatic reactions. However, the mechanism controlling the progress of the overall maturation process has not yet been clarified. Scientists in the research group determined the steric structure of the complex of the tRNA and archaeal Trm5 (aTrm5), an enzyme involved in the maturation of tRNA. They clarified the functions of aTrm5, namely, it induces modification (methylation) of tRNA to promote the accurate mapping of genetic information and also determines whether the steric structure of tRNA has been correctly formed. tRNA with an incomplete steric structure cannot correctly decode genetic information, leading to its inability to mediate the synthesis of proteins or to the synthesis of incorrect proteins. Therefore, tRNA with a correctly formed steric structure should be selected and applied to the mapping of genetic information to ensure the accurate decoding of genetic information. Previously, various control mechanisms during the conversion from genetic information into proteins were clarified. The control mechanism found in this research is completely new; specifically, the accurate conversion from genetic information into proteins is ensured by checking the steric structure of tRNA, which serves as an adapter. The achievements of this research are also expected to clarify the mechanisms underlying diseases associated with tRNA. This research was carried out as part of the Targeted Proteins Research Program, and the results were published in the online version of the American scientific journal, Nature Structural & Molecular Biology (13 September in the US, 14 September in Japan), prior to publication in the printed version (1 October 2009). Publication: |
<Figure>
Fig. 1 Maturation of tRNAThe precursor tRNA forms a stable L-shaped structure upon undergoing various modifications. One terminal of the L-shaped tRNA (the anticodon) decodes genetic codes, and the other terminal (the CCA terminal) binds to the amino acid corresponding to the anticodon. The corner indicated by the red dotted circle is the least stable region in the incompletely modified tRNA. Therefore, the correctness of the formation of this region is an indicator of the completeness of the L-shaped structure.
Fig. 2 Steric structure of aTrm5-tRNA-AdoMet complexIt was clearly observed that aTrm5 recognizes the L-shaped structure of tRNA (indicated by the green ribbon). aTrm5 is composed of three structural domains: D1 (pink), D2 (blue), and D3 (light blue); D1 and D2 are connected by a linker (purple), which has no fixed structure. The methylated tRNA site (next to the anticodon) and the methyl donor AdoMet are in green and yellow, respectively.
Fig. 3 System for checking L-shaped structure of tRNA by aTrm5aTrm5 cannot bind to tRNA before the L-shaped structure has been formed owing to the incomplete maturation of tRNA. Even when the L-shaped structure has nearly been formed, D1 still cannot bind to tRNA when the modification is still incomplete and the corner of the L-shaped structure is not yet distinguishable; therefore, the entire aTrm5 cannot bind to tRNA. After the complete formation of the L-shaped structure, i.e., its corner is clearly distinguishable, D1 can bind to tRNA, increasing the compatibility between aTrm5 and tRNA. Thus, aTrm5 induces a modification (methylation) of tRNA. That is, aTrm5 has a control system to induce modification only when tRNA has the complete L-shaped structure.
<Glossary>
*1 Transfer RNA (tRNA)
Genetic information is stored as a set of codes of triplet nucleic acids (genetic codes) that specifies one amino acid. tRNA is a molecule that acts as an adapter during the translation from such genetic codes to amino acids. These amino acids link to each other to form proteins in the ribosomes of living organisms, where proteins are synthesized.
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- Clarification of New Control Mechanism for Correct Mapping of Genetic Information -An enzyme ensuring the correct formation of the steric structure of transfer RNA was found - (Press Release)