RNA metabolism during cellular transition

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06065
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Kami Daisuke 京都府立医科大学, 医学(系)研究科(研究院), 講師 (80415588)
• Co-Investigator(Kenkyū-buntansha): 秋光 信佳 東京大学, アイソトープ総合センター, 教授 (40294962) ; 五條 理志 京都府立医科大学, 医学(系)研究科(研究院), 教授 (90316745)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: RNA metabolism / Cellular transition / FAPS / RNA-seq / LC-MS/MS

Outline of Final Research Achievements

This study clarified the role of RNA metabolism in differentiation and transformation, and demonstrated that the loss of old trait RNA in the P-body, which plays a central role in RNA metabolism, especially in RNA decay, is essential for the differentiation process. Using A549, we analyzed RNA in the P-body during EMT by RNA-seq and analyzed the changes in RNA present. The RNA in the P-body changed drastically during the differentiation process. In a model of adipogenic differentiation from 3T3-L1 to adipocytes, Ddx6, one of the P-body component proteins, plays an important role in adipogenic differentiation, and its KO suppressed the induction of adipogenic differentiation. In addition, comprehensive gene expression analysis by RNA-seq showed that Ddx6-KO maintained the expression of RNA encoding old traits and Dlk1, a suppressor of adipogenic differentiation. We found that degradation of multiple RNAs that maintain progenitor cell traits, but not removal of suppressors, is important.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は転写されたRNAが細胞内でどのように代謝されているかに着目している。今回、我々はRNA代謝の中心となるP-body内のRNAに着目し、EGFP-DDX6を融合し、P-body内のRNAの変化を解析した。また脂肪分化誘導時におけるP-body形成とDDX6の重要性についても証明しており、細胞内のRNA代謝が重要であることも証明した。以上の結果は、分化制御機構にRNA代謝が能動的に関与する重要な知見であり、発生過程におけるダイナミックな分化制御へのより深い理解に寄与すると共に、癌化の新たな創薬ターゲットとなり得ることを示唆しており、社会的意義は極めて大きいと考える。