2020 Fiscal Year Final Research Report

Regulation of CCN2 by an endogenous UTR blocker and its biological significance

Research Project

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Project/Area Number	19K22716
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 57:Oral science and related fields
Research Institution	Okayama University
Principal Investigator	Kubota Satoshi 岡山大学, 医歯薬学総合研究科, 教授 (90221936)
Co-Investigator(Kenkyū-buntansha)	西田崇岡山大学, 医歯薬学総合研究科, 准教授 (30322233) 服部高子岡山大学, 医歯薬学総合研究科, 助教 (00228488) 高江洲かずみ (河田かずみ) 岡山大学, 医歯薬学総合研究科, 助教 (10457228) 滝川正春岡山大学, 医歯薬学総合研究科, 教授 (20112063) 青山絵理子岡山大学, 医歯薬学総合研究科, 助教 (10432650)
Project Period (FY)	2019-06-28 – 2021-03-31
Keywords	CCN2 / lncRNA / antisense RNA / gene regulation / skeletal development
Outline of Final Research Achievements	The CCN2 gene is expressed in chondrocytes and plays a critical role in mammalian skeletal development. The aim of this study is to clarify the function of a novel lncRNA entitled ACUR that covers the entire 3'-untranslated region of the CCN2 mRNA. First, we found that ACUR was expressed, not only in several types of cancer cells, but also in human chondrocytic cells and chondrocytes isolated from knee joints. ACUR expression was subsequently confirmed in a murine mesenchymal stem cell-like cells, which was repressed along with adipogenic differentiation. Interestingly, CCN2 mRNA expression was decreased upon adipogenic differentiation as well. ACUR was also detected in murine chondroblastic cells. However, in contrast, ACUR expression was increased during the course of chondrocytic differentiation. These findings indicate that ACUR is conserved between human and murine species and that this lncRNA contributes to chodrocytic differentiation, positively regulating the CCN2 gene.
Free Research Field	硬組織生物学
Academic Significance and Societal Importance of the Research Achievements	転写後調節に重要な3'-UTRを覆ってしまうACURはアンチセンスRNAの中でも特殊である。lncRNAの多くは転写因子やクロマチン制御因子を招いて周囲の転写に影響を与えるが、ACURはこれらとは異なる。つまり本研究は新たなlncRNAカテゴリーを見出しlncRNAタキソノミーを塗り替えようとする挑戦である。またアンチセンスRNAの存在が知られる前は、mRNAとアンチセンスRNAの総和を目的mRNA量だと勘違いしていたケースが想定される。そして研究者は遺伝子ノックアウトの際、アンチセンス側に与える影響を十分に考慮してきただろうか？本研究は既存の研究成果に再検討の必要性を認識させるものでもある。