Parametric control of sleep, metabolism, and body clock via translation rate control

2022 Fiscal Year Final Research Report

• Project Area: Parametric biology based on translation rate regulatory mechanism
• Project/Area Number: 20H05783
• Research Category: Grant-in-Aid for Transformative Research Areas (B)
• Allocation Type: Single-year Grants
• Review Section: Transformative Research Areas, Section (III)
• Research Institution: Kyoto University
• Principal Investigator: Doi Masao 京都大学, 薬学研究科, 教授 (20432578)
• Project Period (FY): 2020-10-02 – 2023-03-31
• Keywords: 体内時計 / 翻訳 / uORF / 体温

Outline of Final Research Achievements

In order to maintain health in an environment that changes dramatically from day to night, the 37 trillion cells in the body need to synchronize their rhythmic tempo, rather than being separated from each other. It has been shown that changes in basal body temperature at the level of a few degrees Celsius contribute to the harmonization of rhythms throughout the body, but the molecular mechanism has not been clarified. In this context, we have identified a new RNA element called uORF in the 5'UTR of the clock gene Per2 and showed that it is essential for cellular clock temperature entrainment (Cell Rep 2023). The uORF-mediated translational control of Per2 was important for efficient skin wound healing and therefore can be considered to be medically important (The Science News 3/17/2023).

Free Research Field

時間生物学

Academic Significance and Societal Importance of the Research Achievements

全身の体内リズムの不調和は、多くの病気の原因になることが知られている。したがって、今回の生理的体温変動への体内時計の調和を仲介するRNAエレメントの発見は、全身の細胞リズムの調和に基づいた新しい治療薬の開発の土台につながなる可能性がある。また今回の発見は、翻訳のスピード調節をつかさどるRNA配列uORFの生体における役割を動物個体レベルで明らかにした初めての例であり、その学術的および社会的重要性からJSTの海外向け科学ニュースサイト「Science Japan」においても本研究の成果が紹介された（https://sj.jst.go.jp/news/202304/）。