Internal Ribosome Entry Site (IRES)是位於啟始密碼子上游的調控元件(cis-acting element)，能直接吸引核醣體複合物來合成蛋白質。經由IRES調控之轉譯機制最先在poliovirus病毒中發現，隨後在細胞內表現的基因也陸續發現具有IRES調控的轉譯機制，例如：Bip、FGF2、 c-myc、p53和HIF-1。截自目前為止，大約有90筆基因帶有IRES，其中大約一半基因屬於致癌基因和生長因子及參與在細胞凋亡(apoptosis)的調控。這也說明了IRES調控之轉譯機制對於維持細胞體內之平衡扮演著重要角色，特別是當cap-dependent轉譯機制被抑制時。因此也讓我們想了解有多少基因帶有IRES的調控元件，並且更進一步想探討IRES在生理功能上的角色。
　　在本論文中，我們利用結構型態比對的軟體來分析人類中可能帶有IRES的基因，將所預測資料存入資料庫且建構了能預測IRES存在與否之整合型的網站，並且將其命名為IRES omnibus (I.O)。由所得的資料中發現，在5’UTR某些區域中會存在有連續不中斷且相互重疊的IRES二級結構，並將這樣特殊區域命名為internal ribosome entry zone (IREZone)。目前我們將系統中的資料劃分為IRES與IREZone兩大組群，其分別約人類基因總數的24.8%與45.6%。利用過去文獻與microarray 資料來驗證所得到之結果，約達80%以上的預測準確性。透過報導基因實驗顯示了IREZone活性高於單一的IRES。此外也證實了AU-rich的IRES的序列同樣具有IRES的轉譯活性，此結果也有別於過去認為IRES大約是GC-rich序列的認知。另一方面於IREZone基因組群中，也分析出兩組調控元件存在於IREZone區域內，分別為(CGG)８重複序列與(CCG)８重複序列。為了進一步找出這些帶有調控元件的IREZone在功能上的角色，透過Ingenuity software將其作系統性分類，其結果也顯示帶有(CCG)８與(CGG)８ 的IREzone基因組別參與在神經相關疾病與癌症，相較於對照組(IREZone基因組群)大都參與在細胞死亡的生理作用，帶有相同調控元件的組別，其調控的功能可能更加一致。
　　綜合上述結果，我們建立了能準確預測IRES的系統，並且也發現了一些有別於過去的概念，例如：IREZone的概念、AU-rich的IRES具有IRES的轉譯活性、帶有相同調控元件的IRES之基因其調控的功能可能更加一致。這樣的分析結果也提供了我們在未來一個新的方向來探索IRES在生理功能上的角色。

Internal Ribosome Entry Site (IRES) is a cis-acting element located at the upstream of the translation codon to recruit the ribosome complex to undergo protein translation. Translation by internal ribosome entry was first identified in poliovirus, but a number of cellular mRNAs containing IRESs have subsequently been found, including basic fibroblast growth factor, c-myc, p53, and HIF-1. Till now, around 90 cellular IRES elements have been identified, almost half found in genes encoding oncogenes, growth factors, and proteins involved in the regulation of apoptosis. This suggests that IRES-dependent translation is an important regulatory mechanism for the maintenance of cellular homeostasis, especially when cap-dependent initiation is inhibited. Therefore, it would be interested to understand how many genes bearing the IRES to elucidate the functional role of IRES.
　　In this study, we use the pattern search algorithm to screen the whole human transcripts to identify the genes bearing the IRES elements. And then the web server of IRES omnibus was established. From the result, a special phenomenon which multiple IRES structures existed in specific region was found, and this region was named as internal ribosome entry zone (IREZone). The total human transcripts were identified to contain the IRES or IREZone element about 24.8% and 45.6%, respectively. The accuracy of our result was proved by the prediction of the reported genes which bearing IRES. Using bicistronic reporter assay, we demonstrated that IREzone exhibited higher IRES activity then single IRES. Furthermore, the Y-shape structure with AU-rich sequence was demonstrated to have IRES activity. This result is different from the normal concept that IRES have highly GC content. On the other hand, we also identified two kinds of sequence motif in genes bearing IREZone, (CGG)８ and (CCG)８. To further characterize the functional role of these motifs. The genes bearing IREZone with these motifs were clustered by Ingenuity software. The majority of genes bearing IREZone were found to involve in the function of cell death. however, the gene bearing (CGG)８ and (CCG)８ motif involved in neurological disease and cancer.
　　Overall, we constructed an integrated web server to predicting the IRES element, and proposed some new concept about the IRES. These results provide us a new way to explore the functional role of IRES in biological process.

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