Nutrient condition and organism lifespan through RNA methylation

2020 Fiscal Year Final Research Report

• Project/Area Number: 17H01519
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied molecular and cellular biology
• Research Institution: University of Tsukuba
• Principal Investigator: Fukamizu Akiyoshi 筑波大学, 生存ダイナミクス研究センター, 教授 (60199172)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: メチル化 / RNA / 寿命 / 線虫

Outline of Final Research Achievements

This study focused on the methyl donor S-adenosylmethionine that is produced through the methionine cycle and aimed to elucidate the molecular mechanism underlying the relationship between nutrient condition and organism lifespan from the viewpoint of RNA methylation. By using Caenorhabditis elegans as an aging model, we established a comprehensive analysis of endogenous RNA methylation. Briefly, total RNA of C. elegans was separated into low molecular weight RNA fraction, 26S and 18S rRNAs, then these were digested by nuclease/phosphatase, and the yielded methylnucleosides were quantitatively analyzed by using LC-MS/MS. We also identified a novel RNA methyltransferase and revealed that it is responsible for methylation at N1 of tRNA adenosine 58. Furthermore, we demonstrated that knockdown of this enzyme results in an increased lifespan compared with wild-type. Collectively, these findings suggest a possible involvement of tRNA methylation in the regulation of organism lifespan.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義は、これまで酵素と基質の関係に焦点が当てられてきたメチル化修飾研究の分野において、メチル基供与体という第3のパラメーターの重要性を提唱した点にある。またこのメチル基供与体S-アデノシルメチオニンは、必須アミノ酸であるメチオニンの代謝を経て産生されることから、栄養代謝とメチル化修飾の関係も浮き彫りになった。さらに本研究は、タンパク質の翻訳に必須なトランスファーRNAのメチル化修飾が、生物個体の寿命調節に寄与することも明らかにした。以上の成果は、我が国の課題である健康寿命の延伸に向けて、栄養学の視点からも貢献しうる基礎的知見を提示するものであり、社会的意義を有する。