Identification and function of endogenous retrovirus derived genes that mediate cell fusion

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K19359
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Molecular and Genome biology and related fields
• Research Institution: Tokai University
• Principal Investigator: UEDA Mahoko 東海大学, 医学部, 奨励研究員 (60760353)
• Co-Investigator(Kenkyū-buntansha): 三橋 里美 横浜市立大学, 医学部, 助教 (40466222)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: Endogenous retrovirus / envelope gene / cell differentiation / cell fusion / novel gene

Outline of Final Research Achievements

The purpose of this study is to identify novel genes that directly mediate cell fusion during myoblast and osteoclast differentiation. In these cells, the mutual fusion is indispensable for normal cell differentiation, however the gene that mediate the fusion and the fusion mechanism are unclear. To identify such novel genes, we focused on an envelope domain of endogenous retroviruses (ERV), which have the potential to mediate cell fusion, in mammalian genomes. First, we performed RNA-seq analyses and identified candidates for the envelope-derived genes in mice myoblasts and osteoclasts. After further filtering using protein structures predicted based on candidate sequences, we obtained final candidate sets. Then, we performed siRNA knockdown and over-expression analyses and identified a sequence that showed fusion activity in myoblasts. We are now in the final stage of this project, and confirming the function of the candidates.

Free Research Field

ゲノム比較

Academic Significance and Societal Importance of the Research Achievements

本研究は、分化時の融合細胞で多くの発現解析が行われてきたにも関わらず発見されていない、細胞融合にかかわる直接因子の特定を目指したものである。本研究により、ERV由来の遺伝子が筋細胞・破骨細胞の分化融合にかかわることが明らかになれば、広く細胞融合という現象が、機能の無いと思われてきたゲノム領域にある、外来性の遺伝子により媒介されることを示すことになり、進化遺伝学やゲノム科学の分野に新しい知見をもたらすと考えられる。また今後、ヒトの筋細胞・破骨細胞の分化・融合メカニズムが解明されれば、発症機序が不明な筋再生や骨代謝疾患の治療開発に道を開くことも期待される。