RNA Riboswitch搜尋系統之設計與實作

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姓名

葉記達(Chi-ta Yeh) 查詢紙本館藏

畢業系所

系統生物與生物資訊研究所

論文名稱

RNA Riboswitch搜尋系統之設計與實作
(RiboCatcher: A design and implementation of RNA Riboswitch searching system)

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摘要(中)

Riboswitch是一種近年來發現，對於基因調控相當重要的調控因子，其對於基因表現有其特殊功用和調控方法。由近年來的研究中，我們可以得知各種Riboswitch都有其特殊結構與其特定位置供該riboswitch相應偵測之代謝分子結合。在各Riboswitch中，位於代謝分子與riboswitch之結合位置或者其它位於Riboswitch上有其特殊功能之位置的序列都有一個特性，就是生物演化的過程中，它們比Riboswitch上其它位置的序列擁有更高的保留性。
Riboswitch的核糖核酸二級結構，在演化上是保留性高，而且有其功能性存在的。在Riboswitch中，核糖核酸的二級幹狀結構上面對股上相對兩位置上之核甘，若其中之一突變造成二級幹狀結構的瓦解，會使得Riboswitch失去其與代謝分子的結合能力，因而失去其調控基因的能力。但若對其中之另外一股上的核甘做相對應的突變，使該位置Riboswitch的幹狀二級結構回復，則能夠使得Riboswitch重新得到與代謝分子結合和調控基因的能力，且該能力與其在自然界中存在的未經突變Riboswitch相當。而發生在代謝分子結合點或擁有功能性的位置之單點突變，則大大的降低了Riboswitch的調控能力。因此，我們發現了對於Riboswitch這種調控因子而言，結構與序列保留度擁有同等的重要性。
有鑑於此，我們運用了對於Riboswitch這種調控因子在結構與序列上保留度高的特徵來做為發展Riboswitch預測工具的主要方法。利用此兩種特徵，我們開發了一個針對Riboswitch的搜尋工具與網站以作為研究Riboswitch之用。

摘要(英)

Riboswitches are recently revealed that are important functional and regulatory elements of gene expression. From recent researches, we know that each riboswitch has its unique structure and ligand binding site. Binding sites or other functional sites are more conserved than other non-conserved stem region.
Structure conservation is important and compensatory mutation of stems exhibit transcript activity similar to the wild type in the biological experiments while single point mutation destroy the stem structure of riboswitch and show higher amount of transcript activity than wild type. Mutations of ligand binding site region or functional sites decrease regulating ability of riboswitch. Accordingly, we found that the structure and the sequence conservation are both important in search progress.
As described above, we used the conservation of structures and sequences as characteristics to build our riboswitch prediction system. By using these two characteristics, we developed a riboswitch search tool and a web server for researching of riboswitches.

關鍵字(中)

★ 基因調控
★ 核糖核酸
★ riboswitch
★ RNA

關鍵字(英)

★ riboswitch
★ gene regulatory
★ RNA

論文目次

Table of Contents
Chapter 1 Introduction 1
1.1 Background 1
1.2 Motivation 3
1.3 Goal 4
Chapter 2 Related Works 5
2.1 The riboswitches searching tools 5
2.2 RibEx 5
2.3 Riboswitch Finder 6
2.4 INFERNAL 8
Chapter 3 Materials and Methods 9
3.1 Materials 9
3.1.1 Rfam 9
3.1.2 Literature survey and structure define 10
3.2 Methods 15
3.2.1 Detecting conserved structure 15
3.2.2 HMMER 22
3.2.3 Motif extract and building HMM profiles 22
3.2.4 Model evaluation 26
3.2.5 Free energy checking 28
3.3 Processing flow 28
Chapter 4 Results 30
4.1 Tools and result presentation of our system 30
4.1.1 Tools used to develop our systems 30
4.1.2 Environment of our system 30
4.1.3 The web server and the software package of our systems 30
4.2 The datasets we used while searching process for examine our method 33
4.2.1 Rfam database 33
4.2.2 NCBI sequence database 33
4.2.3 COGs (Clusters of Orthologous Groups) 34
4.3 Search results of Rfam full records 35
4.3.1 Search results of our method and other tools against Rfam full records 35
4.4 Search results of some genomes against Purine riboswitch 40
4.4.1 Complete genomes searched by our method against Purine riboswitch 40
4.4.2 Search results of complete genome by our method against Purine riboswitch 42
4.5 Search results of COGs against Purine riboswitch 48
4.5.1 Dataset which we obtain through COG database 48
4.5.2 Strategies of obtaining data and searching for Purine riboswitch 49
4.5.3 Search results of COG by our method against Purine riboswitch 50
Chapter 5 Discussion 53
5.1 Discuss the search results 53
5.1.1 Sequences missing by our method 53
5.2 Functional comparison with other tools 55
References 57
List of Figures
Figure 1 - Two different regulation mechanisms of riboswitch regulating gene 2
Figure 2 – The structures of each 12 different riboswitches which are plotted by RNALogo (8) 4
Figure 3 - A RibEx search result example (from RibEx website) 6
Figure 4 - An example of Riboswitch Finder search result 7
Figure 5 – An example in Rfam record of seed alignments for PreQ1 riboswitch family 10
Figure 6 - The consensus structure of Purine riboswitch. Circles stand for Watson-Crick base pairs that are weakly conserved in P2 and P3 stems. Asterisks label the nucleotides that may have functional effect. 11
Figure 7 – L2 and L3 have a loop-loop interaction in Purine riboswitch aptamer domain on both ON state or OFF state. The G and HX denote guanine and hypoxanthine, respectively. 12
Figure 8 – Sequence and structure information display by RNALogo (8) 13
Figure 9 – The consensus structure of Purine riboswitch (24,25) 15
Figure 10 – The structure searching algorithm of Purine riboswitch. P1, P2 and P3 are stem 1, stem 2 and stem 3, respectively. The Y (pyrimidine) in the sequence noted the nucleotide position of Purine riboswitch to majoring identify between guanine and adenine. 16
Figure 11 – 4 structure searching type of our method 17
Figure 12 – Types defining to compose the Purine riboswitch, by Type 1, Type 2 and Type 2 structure. 19
Figure 13 - Types defining to compose the Lysine riboswitch, by Type 1, Type 3, Type 2, Type 2, Type 2 and Type 2 structure. 20
Figure 14 - Types defining to compose the ykkC-yxkD riboswitch, by Type 4, Type 3, Type 2 and Type 2 structure. 21
Figure 15 – The conserved ligand binding region and functional sites (24,25) 23
Figure 16 - Motifs we extracts from Rfam records of Purine riboswitch family 25
Figure 17 – HMMER constructs the consensus part of our model 26
Figure 18 – Model evaluation of query sequence 27
Figure 19 – The processing flow of RiboCatcher 28
Figure 20 - Home page of RiboCatcher 31
Figure 21 - The result page of RiboCatcher 31
Figure 22 - The result page with more details by RiboCatcher 32
Figure 23 – Distance between Purine riboswitches and following regulated genes in Rfam dataset (Purine riboswitch seed alignments [22/122]) 44
Figure 24 – Rfam records and other tools miss in searching riboswitches of containing compensatory mutation 46
Figure 25 – The loop sequence of consensus Purine riboswitch and putative Purine riboswitches missed in Rfam records and other tools 47
Figure 26 – Compare the conservation of 3 putative Purine riboswitches which are found by our method with Rfam seed records of Purine riboswitch by using RNALogo 48
Figure 27 – Gene numbers of different COG groups 49
Figure 28 – Acquire the 5’-UTR sequence and 3’-UTR sequence of genes recorded in the COGs databases 50
Figure 29 – The consensus structure of coenzyme B12 (Cobalamin) riboswitch 54
List of Tables
Table 1 – Comparison of our method searching results with other tools against Rfam full dataset 35
Table 2 – Structure search result by our method in loose and strict descriptors 37
Table 3 – Search results against Rfam seed and full records by our method of strict and loose descriptors 39
Table 4 - The genomes that we used in our search process 41
Table 5 – The search result of Purine riboswitch on chosen organisms of Firmicutes in the Table 4 43
Table 6 – The search result of our method against COGs database 51
Table 7 – The comparison with other tools 55

參考文獻

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指導教授

洪炯宗、吳立青
(Jorng-tzong Horng、Li-ching Wu)

審核日期

2008-7-14

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