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  • 學位論文

辨識人類、黑猩猩、老鼠及大鼠的 MicroRNA 核心啟動子

Identification of MicroRNA Core Promoters in Human, Chimp, Mouse, and Rat

指導教授 : 吳家樂
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摘要


目的:微核醣核酸 (miRNA) 是一種短的非編碼 RNA 序列。在調控目標基因方面,它們是扮演重要角色的單股 RNA。因為 miRNA 基因的轉錄機制是 miRNA 合成的第一步,也是最重要的一步,因此本篇論文將聚焦於這個議題上。對於 miRNA 的轉錄其實所知有限,因此我們將著重於 miRNA 基因的上游區域分析,並試著找出轉錄因子結合位置 (transcription factor binding sites, TFBS)。 方法:我們選定了四個物種(人類,黑猩猩,老鼠,以及大鼠)來加以分析其 miRNA 基因的上游序列2000 bps。我們使用的工具為 Tmod (Toolbox of Motif Discovery) 來搜尋有意義的序列功能域 (motifs)。找出幾個顯著的 TFBS 後,會更進一步地比較四個物種有哪一些 TFBS 是共有的。最後找出共同調控這四個物種的轉錄因子 (transcription factor, TF) 以及使用 motifs 的資訊來了解這些物種於演化上的關係。 結果和結論:我們在這四個物種之中,找出出現頻率最高,具有保留性的四個轉錄因子,以及根據 motifs 得到的演化樹,判斷 motifs 在物種演化上所具有的意義。

並列摘要


Objectives: MicroRNAs (miRNAs) are a class of short, noncoding RNA sequences. In genetics, they are single-stranded RNA molecules which play important roles in the regulation of target genes. Because the transcriptional mechanism of miRNAs is the first, important step of miRNAs biogenesis, we should get a better knowledge about it. We have limited understanding of the transcription of miRNAs so we want to analyze the upstream sequences of miRNA genes to identify putative transcription factor binding sites (TFBS). Methods: We chose four species, including human, chimp, mouse, and rat, to analyze their upstream sequences. Promoter prediction tool, Tmod (Toolbox of Motif Discovery) was employed to search for significant motifs in these sequences. After finding out several significant TFBS, we further identified which motifs are conserved across the four species. Finally, it is found that certain transcription factors (TFs) is responsible for the regulation of miRNA genes, and motifs information are further used for the evolutionary relationship study. Results & Conclusions: It is found that four TFs are conserved across the four species, and we also estimated the significance of their binding motifs in evolution through phylogenetic study.

參考文獻


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