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  • 學位論文

人類mRNA多聚腺甘酸化作用點之特徵探勘與預測

Characterization and prediction of mRNA polyadenylation sites in human genes

指導教授 : 洪炯宗
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摘要


mRNA 的多聚腺甘酸化(polyadenylation)在真核細胞中是一項必要的反應,未成熟的mRNA 藉由此反應形成3 碳糖尾端,並且多方面影響了mRNA 的新陳代謝。然而由於多聚腺甘酸化對於其作用點具有多重的選擇性,其中存在著複雜的機制,至今尚未被完全了解。DNA 可以經由選擇性的多聚腺甘酸化,轉錄生成的不同蛋白質產物,藉此針對特定組織或生長時期進行調控的工作。如此機制的運作不良可能導致疾病的產生。多聚腺甘酸化的作用點需要藉由鄰近序列上或結構上的特徵得以成功被相關因子所辨識,包括某些已知的蛋白質與序列之結合。經由對多聚腺甘酸化的作用點的特徵探勘我們發展了一個可靠的預測模型,以幫助探究這項機制的奧秘。此外,我們使用現有的結構預測軟體,初步探討了RNA 二級結構對於多聚腺甘酸化的影響。我們發現一種簡單的二級結構以顯著的比例出現在作用點附近。如此一項功能性的結構特徵值得後人深入研究。

關鍵字

多聚腺甘酸化 預測

並列摘要


mRNA polyadenylation is the essential cellular process by which most eukaryotic pre-mRNAs form their 3’ ends. It has been shown to influence many aspects of the cellular metabolism of mRNA. The complexity of mRNA polyadenylation mechanism mainly lies in the selection of poly(A) sites, since polyadenylation itself could be a regulated event. The event of alternative polyadenylation has been shown to be widespread. In this study, we developed a reliable methodology for poly(A) site prediction via bioinformatic characterization of poly(A) sites. We also conducted a series of observations on the impact of RNA structure in a preliminary step and found a significant usage of hairpin structure by using motif search tools. Thus, we suggest that in addition to the sequence pattern around poly(A)sites, there exists a widespread structural pattern employed by human mRNA polyadenylation.

參考文獻


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