Molecular analyses of tRNA mimicry proteins for alternative mRNA decoding in protein synthesis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H04760
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Ito Koichi 東京大学, 大学院新領域創成科学研究科, 教授 (10262073)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: リボソーム / 翻訳制御 / 品質管理 / 遺伝暗号 / 分子擬態

Outline of Final Research Achievements

In addition to the nucleic acid molecule tRNA, which is an adapter molecule in genetic decoding for sense codons, for decoding mRNA by ribosomes in protein synthesis, a set of tRNA mimicry proteins are known, such as for the decoding of translation termination codon and for the rescue of ribosomes stalled on aberrant mRNA. In this study, by comparative analysis of both eukaryotic and bacterial tRNA mimicry proteins, we have demonstrated the novel functionality of a eukaryote specific GTP binding protein, Ski7. We also succeeded in finding novel ribosome rescue mechanism including the poly peptide-chain release factors (eRF1/eRF3) that has not been reported so far in eukaryotes.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

mRNAからのタンパク質合成の高次機能発現制御機構の解明は、生命に普遍的な分子機構の理解のみならず、新規機能性タンパク質の人工合成方法の開発や癌をはじめとする多くの遺伝疾患の発症機構の解明や創薬・治療方法の開発に必須な知見となる。本研究成果は、細胞内におけるタンパク質合成におけるリボソームの翻訳反応に関わりその高次機能発現への拡張を可能にするtRNA擬態タンパク質による高次機能発現機構の分子メカニズムの解明により、その医工学的応用研究への手がかりを与えた。