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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 張智芬(Zee-Fen Chang) | |
dc.contributor.author | Tsung-Han Lu | en |
dc.contributor.author | 呂宗翰 | zh_TW |
dc.date.accessioned | 2021-06-15T01:22:44Z | - |
dc.date.available | 2009-09-15 | |
dc.date.copyright | 2009-09-15 | |
dc.date.issued | 2009 | |
dc.date.submitted | 2009-07-24 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42770 | - |
dc.description.abstract | 人類胸腺嘧啶激酶(human thymidine kinase1, hTK1)是負責dTTP生合成 salvage 路徑中的重要酵素,其表現量及活性隨細胞週期的進行而變化;此嚴密的週期性調控乃是藉由不同層面之調節而達成,其中包含轉錄效率的改變、後轉譯蛋白修飾及寡聚化狀態之轉變(oligomerization status)等方式。此外,後轉錄調控,為另一項重要的調控方式,但是其詳細分子機制至今未明;因而本篇論文便針對此議題進行深入的研究與探討。
過去許多研究皆顯示,存在於mRNA中以供辨認的調節元素(regulatory element) 大多坐落於其非轉譯區(untranslated region, UTR);同時根據hTK1 mRNA帶有相當長度3’UTR之特性,本研究首先探討hTK1 3’UTR在後轉錄調控中扮演的腳色。實驗利用大腸癌細胞株(HCT116)進行冷光酶分析試驗(Luciferase reporter assay),結果顯示,當螢光基因3’端帶有hTK1 3’UTR時,其冷光表現量便會大幅受到抑制然而mRNA卻無相對的變化,顯示此區塊對後轉錄調控之重要性。 在後轉錄調控中,3’UTR是微型核糖核酸(microRNAs, miRNAs)後轉錄調控的重要辨識區塊。因此我們藉由hTK1 3’UTR 的序列分析,找出兩個可能之miRNAs 標的位置(target sites), miR512-5p及 let-7/ miR98;並且將兩個標的序列分別突變後進行分析試驗。結果發現兩種突變皆能減弱hTK1 3’UTR所造成的抑制效果;此外,miR512-5p及 let-7/ miR98 的大量表現也能藉由相對應之標的位置抑制冷光活性的表現。 最終,我發現在HCT116 p53(-/-)細胞中,若表現miR512-5p之反向核酸序列(anti-sense)便能夠大量提升hTK1蛋白質的表現量。 | zh_TW |
dc.description.abstract | Human thymidine kinase1 (hTK1), is a key enzyme in the salvage pathway of dTTP synthesis, and its expression and activity were strictly regulated during the cell cycle. The stringent control of hTK1 is regulated at different levels, including transcription and posttranslation by protein modification and oligomerization. However, posttranscriptional control is another important regulation of hTK1 while its molecular mechanism remains unclear. Thus, the specific aim of this thesis work is to investigate this unknown mechanism.
Many studies have revealed that most of the regulatory elements within mRNAs were located in the untranslated regions (UTRs). Since a long 3’UTR is present in hTK1, we first proposed and examined the importance of hTK1 3’UTR in posttranscriptional regulation. By the reporter luciferase assay in HCT116 cells, I found that hTK1 3’UTR conferred the reporter a repression effect. Because of the importance of 3’UTR in miRNAs, the sequence analysis was performed to find potential miR512-5p and let-7/ miR98 target sites. Mutation was introduced to each target sites of hTK1 3’UTR for reporter assay, and the results showed that each mutation relieved hTK1 3’UTR-mediated reporter repression; furthermore, overexpression of miR512-5p and let-7/ miR98 also repressed reporter activity through the corresponding target site. Finally, I found that the expression of anti-sense of miR-512-5p was able to significantly elevate the endogenous expression of hTK1 in HCT116 p53 (-/-) cells. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T01:22:44Z (GMT). No. of bitstreams: 1 ntu-98-R96442008-1.pdf: 1789311 bytes, checksum: fa1ac6e3b84385e73880748448e4fbcb (MD5) Previous issue date: 2009 | en |
dc.description.tableofcontents | 中文摘要...........................................2
Abstract............................................4 Introduction .......................................6 Materials and Methods.......................18 Results.............................................26 Discussion........................................31 Figures.............................................35 References........................................49 | |
dc.language.iso | en | |
dc.title | 人類胸腺嘧啶激酶後轉錄調控機制之探討 | zh_TW |
dc.title | Posttranscriptional regulation of human thymidine kinase1 | en |
dc.type | Thesis | |
dc.date.schoolyear | 97-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 李芳仁(Fang-Jen Lee),張明富(Ming-Fu Chang),鄧述諄(Shu-Chun Teng),羅?升(Wan-Sheng Lo) | |
dc.subject.keyword | 胸腺嘧啶激酶,後轉錄調控,3’非轉譯區,微型核糖核酸, | zh_TW |
dc.subject.keyword | Thymidine kinase1 (TK1),Posttranscriptional control,3’ untranslated region (3’UTR),microRNA (miRNA), | en |
dc.relation.page | 56 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2009-07-24 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
顯示於系所單位: | 生物化學暨分子生物學科研究所 |
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