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系統識別號 U0026-2607201017114900
論文名稱(中文) 核酸結合蛋白在基因表現中所扮演功能角色的系統性分析
論文名稱(英文) Systematic analysis of the functional role of different RNA-binding proteins in gene expression
校院名稱 成功大學
系所名稱(中) 生物資訊研究所
系所名稱(英) Institute of Bioinformatics
學年度 98
學期 2
出版年 99
研究生(中文) 黃世雯
研究生(英文) Shih-Wen Huang
學號 z2697102
學位類別 碩士
語文別 中文
論文頁數 54頁
口試委員 指導教授-曾大千
口試委員-孫孝芳
口試委員-洪良宜
中文關鍵字 後轉錄調控  核酸結合蛋白 
英文關鍵字 posttranscriptional regulation  RNA-binding proteins 
學科別分類
中文摘要 後轉錄調控(posttranscriptional regulation)對於基因的表現扮演相當重要的角色,後轉錄過程中的每一個步驟都是調控基因產生蛋白質的關鍵點,其中包括了剪接(splicing)、多腺苷酸化(polyadenylation)、編輯(editing)、mRNA的運送、mRNA的降解及轉譯(translation),而在所有這些過程當中,RNA-binding proteins都會參與在其中,來決定它們所結合的RNA的功能與命運。RNA-binding proteins是以其所帶有的RNA-binding domains來辨認並結合目標RNA,但目前為止,還沒有專門針對RNA-binding proteins或RNA-binding domains的資料庫,所以我們想要建立一個RNA-binding proteins相關的資料庫。利用NCBI、UniProt 和 InterPro資料庫,我們篩選出726個RNA-binding proteins與 136種RNA-binding domains,並將這些RNA-binding proteins依照它們所帶有的domains進行分類。接下來我們觀察到參與在相同生物功能的RNA-binding proteins,它們的序列保留程度(conservation)會較高,此外當RNA-binding proteins帶有相似的架構時,它們的RNA-binding domains保留性程度也會較高,我們認為在這些保留的胺基酸當中對於RNA-binding proteins會參與在特定功能中是重要的。更進一步,為了比較各RNA-binding proteins之間基因表現情形的相關性,我們先利用群集分析將RNA-binding proteins分群後再計算各群內成員的相關係數,我們認為表現相關程度愈高的RNA-binding proteins愈有可能參與在共同的調控機制當中。利用本資料庫結合已知的資訊以及材料,使用者可以找到RNA-binding proteins可能的目標、合作的對象、或是RNA-binding domains上重要的胺基酸,提供了研究RNA-binding proteins的相關資料,讓使用者能更迅速找到研究的方向。
英文摘要 Post-transcriptional regulation is essential for ensuring tightly and precisely control of gene expression. It is now widely appreciated that each and every step of post-transcriptional processes, including splicing, polyadenylation, editing, nuclear export, RNA localization, RNA degradation, and translation, can serve as a regulation point to modulate protein production of a particular gene. RNA-binding proteins (RBPs) play essential roles in all of above processing, and regulate the function and fate of the RNA molecular with which they associate. RNA recognition by proteins is primarily mediated by certain classes of RNA binding domains and motifs. At present, there is no RNA-binding proteins-related database, so we intend to construct a database which is specific for RNA-binding proteins and RNA-binding domains. After whole genome screening, 726 RNA-binding proteins and 136 RNA binding domains from NCBI, UniProt and InterPro were collected and classified base on RNA binding domains which they are bearing. And then, the RNA-binding domains participated in the similar biological function are more conserved. Additionally, the RNA-binding proteins bearing similar architecture may bearing more conserved RNA-binding domains. Further more, in order to compare the gene expression profiles between RNA-binding proteins, the cluster analysis to grouping them and correlation coefficient was used. We proposed that the higher the correlation coefficients, the more possible they regulate gene expression corporately. From this database, users could find potential targets or partners of RNA-binding proteins and important residues in the RNA-binding domains. It provides a good way to study the field of RNA-binding proteins.
論文目次 中文摘要………………………………………………………………………I
Abstract …………………………………………………….………………III
誌謝 ……………………………………………………………………..V
圖目錄 …………………………………………………………………….IX
表格目錄 ……………………………………………………………………..X
附錄目錄 …………………………………………………………………….XI


第一章 緒論 1
第一節 後轉錄調控 (post-transcriptional regulation) 1
第二節 RNA-binding Proteins 3
第三節 RNA-binding proteins相關研究 5
第四節 研究動機 7
第二章 實驗方法 9
第一節 資料收集與來源 9
第二節 資料建立與分類 10
第三節 電腦環境 11
第四節 生物資訊相關工具 11
第五節 統計方法 12
第三章 實驗結果 13
第一節 資料庫系統架構與分析 13
第二節 RNA-bind domains在功能上的序列保留性(conservation) 14
第三節 結構類似之RNA-binding proteins的序列保留性 16
第四節 RNA-binding proteins之間的關係 17
第五節 資料庫的應用—HuR 18
第四章 討論 21
第一節 RNA-bind domains的保留性(conservation) 21
第二節 RNA-binding proteins的表現相關性 22
第三節 HuR的新發現 23
第五章 參考文獻 25

圖目錄
圖一、 RBPDB系統架構圖 32
圖二、 MEME針對帶有double-strand RNA-binding domain的序列比對結果 33
圖三、 帶有Surp domain之RNA-binding proteins的序列保留性 34
圖四、 ELAV family帶有三個具高度保留性的RNA-recognition motifs 36

表格目錄
表格一、 帶有double-strands RNA-binding domain的RNA-binding proteins與其功能及domain位置 38
表格二、 Surp domain伴隨其他domain一起出現 41
表格三、 表現高度相關的RNA-binding proteins 42
表格四、 ELAV family上的RNA-recognition motif位置 44

附錄目錄
附錄一、後轉錄調控(Post-transcriptional Regulation) 45
附錄二、”RNA binding”的母類別 47
附錄三、”RNA binding”的子類別 52
附錄四、Panther資料庫對”biological process”的註解 54
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