Biosynthesis and function of a novel tRNA modification ectopically acquired by a disease associated mutation

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21243
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 37:Biomolecular chemistry and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Suzuki Takeo 東京大学, 大学院工学系研究科(工学部), 講師 (90533125)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: tRNA / ミトコンドリア

Outline of Final Research Achievements

Structural analyses enabled us to predict a chemical structure of the novel modification found in human mitochondrial tRNA-Met with a pathogenic point mutation. We also predict a modifying enzyme based on the structure and demonstrated that the enzyme can reconstitute the modification in cells by over expression and in vitro by using recombinant protein. To perform ribosome binding assay for measurement of the modification’s decoding ability, we optimized the reaction condition of the assay by using anticodon stem-loop (ASL) as a model tRNA substrate. Although the binding efficiency still did not increase much, the assay condition was finally determined.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

疾患点変異に伴い変異部位と異なる位置に新たに獲得されたRNA修飾は、新規な化学構造を持っていた。このことはヒトにおけるRNA修飾の構造や機能の多様性を表していると言える。当該修飾は疾患を亢進する役割を持つと考えらえることから、今回特定された生合成経路を阻害することが、点変異に起因する疾患の治療や予防につながるといった応用が機体される。