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標題: | 透過人類微生物體尋找伊波拉病毒 microRNA 標的基因 On revealing the gene targets of Ebola virus miRNAs involved in human skin microbiome |
作者: | Pei-Chun Hsu 徐霈君 |
指導教授: | 趙坤茂(Kun-Mao Chao) |
共同指導教授: | 黃俊銘(Chun-Ming Huang) |
關鍵字: | 伊波拉,微生物體, Ebola virus,microbiome,microRNA,THSD4, |
出版年 : | 2018 |
學位: | 博士 |
摘要: | 埃博拉病毒(Ebola virus),是絲狀病毒科的其中一種由鏈狀的負鏈核糖核酸病毒粒子構成,可導致伊波拉出血熱具有高死亡率。埃博拉病毒的組織病理學和免疫病理學上的分析皆顯露,在皮膚組織上的組織病變,與不同程度的內皮細胞膨脹和壞死有所關聯。微生物在宿主內的交互作用在皮膚免疫防線扮演關鍵的角色,而在埃博拉病毒中發現的微小 RNA (miRNAs)暗示著在埃博拉病毒傳染期間所觀察到的免疫逃脫,內皮細胞破裂,以及組織溶解等現象,是埃博拉病毒微小 RNA 造成的影響。 正常皮膚角質細胞( Keratinocytes) 在細胞免疫反應的起始階段可以透過thrombospondin 蛋白質家庭的幫助來進行附著和轉移,許多微小 RNA 已知可以與thrombospondin RNA 的 3 端非轉譯區域結合,從而控制 thrombospondin 蛋白質的穩定性和轉譯行為。 在本篇研究中,我們利用生物資訊學方法尋找痤瘡丙酸桿菌( Propionibacterium acnes)中的短片段 RNA,並發現這些短片段 RNA 也許與微小 RNA 具有相同的功能,我們也尋找出這些 RNA 片段的共同標的基因( target gene)。 這些 RNA 片段傾向於結合在同一 thrombospondin 蛋白質之上,並進行基因表現之調控, 這個現象強調埃這些在博拉病毒、痤瘡丙酸桿菌和人類中的微小RNA 有可能存在潛在性的協同作用。這個結果揭露 thrombospondin 蛋白質與微小RNA 在埃博拉病毒傳染機制中存在重要線索。 Ebola virus, a negative-sense single-stranded RNA virus, causes severe viral hemorrhagic fever and has a high mortality rate. Histopathological and immunopathological analyses of Ebola virus have revealed that histopathological changes in skin tissue are associated with various degrees of endothelial cell swelling and necrosis. The interactions of microbes within or on a host are a crucial for the skin immune shield. The discovery of microRNAs (miRNAs) in Ebola virus implies that immune escape, endothelial cell rupture, and tissue dissolution during Ebola virus infection are a result of the effects of Ebola virus miRNAs. Keratinocytes obtained from normal skin can attach and spread through expression of the thrombospondin family of proteins, playing a role in initiation of cell-mediated immune responses in the skin. Several miRNAs have been shown to bind the 3′ untranslated region of thrombospondin mRNA, thereby controlling its stability and translational activity. In this study, we discovered short RNA sequences that may act as miRNAs from Propionibacterium acnes using a practical workflow of bioinformatics methods. Subsequently, we deciphered the common target gene. These RNA sequences tended to bind to the same thrombospondin protein, THSD4,emphasizing the potential importance of the synergistic binding of miRNAs from Ebola virus, Propionibacterium acnes, and humans to the target. These results provide important insights into the molecular mechanisms of thrombospondin proteins and miRNAs in Ebola virus infection |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/69674 |
DOI: | 10.6342/NTU201800830 |
全文授權: | 有償授權 |
顯示於系所單位: | 生醫電子與資訊學研究所 |
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