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系統識別號 U0026-0812200913423857
論文名稱(中文) UTRHairpin:未轉譯區的髮夾形結構資料庫
論文名稱(英文) UTRHairpin:Untranslated Region Hairpin Structure Database
校院名稱 成功大學
系所名稱(中) 資訊工程學系碩博士班
系所名稱(英) Institute of Computer Science and Information Engineering
學年度 95
學期 2
出版年 96
研究生(中文) 陳建谷
研究生(英文) Chien-Ku Chen
電子信箱 panda@ms82.url.com.tw
學號 p7694143
學位類別 碩士
語文別 中文
論文頁數 59頁
口試委員 指導教授-蔣榮先
指導教授-曾大千
口試委員-辛致煒
口試委員-阮雪芬
口試委員-黃宣誠
中文關鍵字 資料庫  後轉錄調控機制  未轉譯區  調控模體  髮夾形結構 
英文關鍵字 untranslated region  UTR  post-transcription  database  hairpin structure  regulatory motif 
學科別分類
中文摘要 後轉錄調控機制的基因表現通常藉由調控模體(regulatory motif)和特定調控蛋白(regulatory protein)的結合與否來控制該基因的蛋白質合成速率。大部分調控模體位於mRNA的5′或3′未轉譯區(untranslated region),並且具有一級序列和二級結構的雙重特性。因為具有雙重特性的關係,增加了找尋調控模體的困難度。欲對多個物種的未轉譯區找出「可能」為調控模體的序列,是一項困難且計算量相當龐大的工作。許多文獻指出大部分的調控模體為一個穩定的hairpin結構,某些hairpin結構的loop序列會吸引特定調控蛋白與其結合。我們依據以上特性為基礎建立一套處理方法,從多個物種的未轉譯區找出穩定的hairpin結構,建立成資料庫—UTRHairpin。設計了以loop序列為標記的查詢功能,使用者可以透過UTRHairpin找尋高保留性的hairpin結構或是在功能相似的基因中找尋共同hairpin結構。透過UTRHairpin建立的查詢功能可以快速找到一群擁有相同或相似loop序列的hairpin結構而且生理反應相似的基因,該結構可能控制這群基因的基因表現。例如:我們從UTRHairpin找到兩個跟鐵離子運輸有密切關係的基因:transferrin receptor和hemochromatosis,並且發現它們的3′未轉譯區存在某兩個hairpin結構的loop序列是相同,該hairpin結構很有可能控制鐵離子運輸反應。我們試圖建立一個位於未轉譯區的穩定hairpin結構資料庫,生物學家可以透過UTRHairpin所提供的查詢功能,找出「可能」為調控模體的hairpin結構,並且進行實驗驗證,讓後轉錄調控機制更為清楚,對於人類的疾病瞭解和製藥有莫大的幫助。UTRHairpin現在可以進行線上查詢,資料庫網址:http://140.116.247.51/UTRHairpin/。
英文摘要 Post-transcriptional regulatory mechanism of gene expression is accomplished by RNA binding proteins (RBPs) recognizing and binding regulatory motifs to influence the translation of RNAs. Most of regulatory motifs are discovered in 5′ or 3′ untranslated regions(UTRs)of mRNAs, and have characteristics of evolution conservation both in primary sequences and secondary structures. As the result of particular characteristics, it becomes a very arduous task to find regulatory motifs. It is also time-consuming to search for 「possible」 regulatory motifs in UTRs of mRNAs from the whole genome sequences of various species. Numerous papers have concluded that most of the regulatory motifs are stable hairpin structures in UTRs. Moreover, it has been proven that the loop sequences of some hairpins play an important role of inducing regulatory proteins to recognize and bind on the hairpin structures. Base on the biological evidences, we propose a method for exploring stable hairpin structures from UTRs across species, and construct a database, UTRHairpin, to provide the function of searching hairpins across species. Users can search for highly conserved hairpins among genes with similar functions by querying loop sequences. UTRHairpin provides the searching functions of retrieving group of genes which have similar secondary structures or analogous physiological reactions that caused by particular loop sequences. For example, we perform a query in UTRHaipin and discover that transferrin receptor(TFRC)and hemochromatosis(HFE)are both related to transport iron ion in cells, and have two stable hairpin structures with same loop sequence in the 3′UTR, which are possibly corresponding to the regulation of iron ion. Biologists can search in UTRHairpin to obtain hairpin structures which have similar loop sequences and then verify whether these hairpins have similar functions by biological experiments. The major contribution of UTRHairpin is to provide a platform of across species searching of hairpins with possible similar functions, which helps the understanding of Post-transcriptional regulatory mechanism and make progress of understanding the human diseases. UTRHairpin is now on-line and the address is http://140.116.247.51/UTRHairpin/.
論文目次 第一章 導論 1
1.1 背景 1
1.2 研究動機 12
1.3 解決方法 13
1.4 論文架構 13
第二章 文獻回顧與相關研究 14
2.1 從多個物種中找尋調控模體 14
2.2 找尋多條序列的共同結構 16
2.3 調控模體資料庫 17
2.4 基因本體論(Gene Ontology) 21
第三章 基於序列和結構雙重特性的找尋調控模體處理方法 24
3.1 研究假說 24
3.2 UTRHairpin資料庫建立流程 25
3.2.1 UTRHairpin資料庫架構概述 25
3.2.2 資料收集與找尋穩定二級結構的處理方法 26
第四章 實驗設計與結果分析 35
4.1 滑動視窗長度對於預測二級結構正確性的影響 35
4.2 為何使用兩種RNA分子二級結構預測軟體? 39
4.3 利用IRE驗證UTRHairpin資料庫的正確性 41
4.4 從功能相似度較高的基因群找出loop序列相同的hairpin結構 43
4.5 UTRHairpin資料庫操作流程 50
第五章 結論與未來研究方向 53
5.1 結論 53
5.2 未來研究方向 54
參考文獻 55
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