Cooperative expression regulation by eukaryotic translation initiation factor eIF4A1 and glutamine metabolism

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15023
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Shichino Yuichi 国立研究開発法人理化学研究所, 開拓研究本部, 研究員 (40748365)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 翻訳 / 代謝 / 翻訳開始 / グルタミン / 次世代シーケンサー

Outline of Final Research Achievements

Cells dynamically regulate translation and metabolism in response to environmental cues, but their cooperation remains unclear. To understand the synergetic regulation of translation and metabolism, this study investigated the molecular mechanisms of the cooperative regulation of eukaryotic translation initiation factor eIF4A1 and extracellular glutamine for the translation regulation of ODC1, the rate-limiting enzyme for polyamine synthesis. Using specific inhibitors, ODC1 was identified as the causative gene of this phenomenon. Reporter assays revealed the essential regions for translational regulation in the ODC1 gene. Furthermore, this study demonstrated that this eIF4A1-mediated regulation was not caused by amino acids in general, but specific for glutamine.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

ポリアミンと呼ばれる生体分子は細胞増殖、免疫、老化など様々な生命現象に重要であり、その合成の異常亢進はがん化と関連があると考えられている。そのため、細胞内のポリアミン量を一定に保つべく、律速段階を担うODC1の発現は何重もの制御を受けている。本研究で明らかとなったODC1の翻訳制御機構はポリアミンを必要とする様々な生命現象で重要な働きをもつ可能性があり、がん治療研究への発展も期待できる。