Biosynthesis and function of characteristic RNA modifications found in human

2017 Fiscal Year Final Research Report

• Project/Area Number: 26702035
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Biomolecular chemistry
• 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): 2014-04-01 – 2018-03-31
• Keywords: tRNA / 修飾酵素 / 生合成 / 遺伝子

Outline of Final Research Achievements

We revealed the biogenesis and physiological function of 5-formylcytidien (f5C) modification specifically found in the wobble position of human/vertebrates mitochondrial tRNA-Met. A metabolic labeling analysis enables us to predict that f5C synthesis initiates methylation of C to 5-methylcitidine (m5C), and then oxidizes m5C to f5C. Actually, we successfully identified the methyltransferase NSUN3 and the oxygenase ALKBH1 and performed in vitro f5C reconstitution by using these enzymes. Knockout cells of each gene exhibited mitochondrial dysfunction and decreased mitochondrial translation in biochemical analyses. As for species-specific modifications other than f5C, in vitro reconstitution or modifying gene identification were achieved. To deeply understand the function of these modifications, further investigations will be required.

Free Research Field

分子生物学