Tackling the Identification of Regulatory Mechanisms Determining Human Morningness/Eveningness Cnronotype Hidden in Non-Coding Genomic Regions

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21426
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
• Research Institution: Kyoto University
• Principal Investigator: Doi Masao 京都大学, 薬学研究科, 教授 (20432578)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: 体内時計 / ノンコーディング

Outline of Final Research Achievements

Ninety-eight percent of the human genome is noncoding sequence that does not code for proteins. Previous studies on sleep and circadian clock by molecular genetics have mainly been based on mutations in coding sites of genes. In this study, we focused on evolutionarily conserved noncoding elements in the intergenic genomic region and the 5'/3' untranslated region of mRNA, and were able to identify elements that may affect the function of the biological clock. In particular, among them, we found a new sequence called minimal uORF, which controls the translation efficiency of clock gene, and were able to show that it is essential for cellular circadian clock entrainment (Miyake et al., Cell Rep 42:112157, 2023; Kagaku Shimbun 2023/3/17).

Free Research Field

時間生物学

Academic Significance and Societal Importance of the Research Achievements

ノンコーディング配列の重要性は主にこれまで進化発生学的な学術的見地において指摘されてきた。これに対し、本研究では、遺伝子間ゲノム領域およびmRNAの5’/3’非翻訳領域において進化的に保存されたノンコーディングエレメントに着目し、その中に体内時計の機能を左右しうる新しいエレメントを（候補を含めて）同定することができた。ノンコーディング配列の役割を日々の個体の活動パターンの制御にまで拡大する発見であり、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」にも本研究の成果が紹介された（https://sj.jst.go.jp/news/202304/）。