Study of molecular mechanisms for translation termination and ribosome recycling by eukaryotic ribosome

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03180
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43010:Molecular biology-related
• 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): 2020-04-01 – 2024-03-31
• Keywords: リボソーム / tRNA擬態タンパク質 / タンパク質合成 / 翻訳終結 / 品質管理 / リボソーム再生反応 / 翻訳再開始反応

Outline of Final Research Achievements

Translation termination, a critical step in protein synthesis in eukaryotes, involves the interplay of various factors, including tRNA-elongation factor complex mimicking proteins (eRF1-eRF3, Pelota-HBS1), ribosome recycling factors, and quality control factors. To unravel the intricate molecular mechanisms underlying this process, we developed genetic screening systems and novel assay systems to monitor ribosome status.
Our investigations led to the identification of novel functional domains on ribosomal factors ASC1 and S20. These domains act in concert to form a binding interface for Hel2, a ubiquitin ligase that targets ribosome-associated proteins for degradation. We propose a novel mechanistic model, highlighting the cooperative role of these newly identified domains.These findings provide significant insights into the molecular basis of translation termination and hold promise for identifying novel drug target to address various human diseases.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

mRNA上の遺伝暗号をタンパク質に翻訳するのは（翻訳反応）、タンパク質合成の中心装置であるリボソームと無数の翻訳関連因子群です。近年、必要なタンパク質を適切に合成するたに、異常な遺伝情報やそこから合成される有害なタンパク質の発現による弊害を抑制する仕組みとして翻訳終結に連動した品質管理機構に関心が高まっています。本研究は、それに関わる基本的な因子群の分子機構の一つを明らかにしました。