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???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
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dc.contributor.advisor | 蔡欣祐(Hsin-Yue Tsai) | |
dc.contributor.author | Ting-Jie Chang | en |
dc.contributor.author | 張筳婕 | zh_TW |
dc.date.accessioned | 2021-06-17T06:41:32Z | - |
dc.date.available | 2018-09-04 | |
dc.date.copyright | 2018-09-04 | |
dc.date.issued | 2018 | |
dc.date.submitted | 2018-08-15 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72421 | - |
dc.description.abstract | REGE-1是一個具有高度物種保留之zc3h12a-like ribonuclease NYN domain的核糖核酸酶,在秀麗隱桿線蟲中扮演著脂質形成之角色。而REGE-1在哺乳動物的同源基因為Regnase-1,目前已知其在許多不同生理途徑中執行功能,如細胞激素(cytokine)的信使核醣核酸(mRNA)之失能反應、脂質形成、血管新生及M2巨噬細胞的極化現象(polarization)。除了細胞激素(cytokine)的信使核醣核酸(mRNA)之降解反應是藉由剪切於3’-UTR上的莖環(stem loop)結構之外,其他三條途徑都是由Regnase-1刺激內質網壓力(ER stress)達成的。生物體在面臨內質網壓力時會引發包含IRE-1、ATF6及PEK-1之三條內質網的未折疊蛋白質反應途徑(UPRER)。
先前研究已發現在rege-1突變之秀麗引桿線蟲中,脂質減少的現象歸因於REGE-1無法使轉錄因子ets-4的信使核糖核酸降解。然而,REGE-1在秀麗隱桿線蟲中是否也參與內質網壓力是目前仍然未知的。 在本篇論文中所使用的rege-1突變種rege-1(tm3682)是第三外顯子及第四外顯子缺失的品種,造成其rege-1基因上出現過早的停止密碼(premature stop codon)。我們發現該如同先前對REGE-1之研究,該品種也有脂質減少的情形。更進一步,為了瞭解REGE-1是否影響內質網的未折疊蛋白質反應途徑,我們使用hsp-4::gfp報導基因以及即時聚合酶鏈鎖反應(RT-qPCR)偵測在衣黴素(tunicamycin)處理前後的蟲之hsp-4及xbp-1s之表現。發現rege-1(tm3682)不論在GFP強度或在hsp-4的表現都較野生型高,但在xbp-1s卻無明顯的差異。而且衣黴素適性測試發現rege-1(tm3682)對內質網壓力的適應性是比較好的。 我們的結果發現REGE-1可能在內質網的未折疊蛋白質反應途徑中及對內質網壓力適應性扮演負調控蛋白的角色。我們的結果將闡明REGE-1是否,以及可能如何調節內質網壓力。 | zh_TW |
dc.description.abstract | REGE-1, a zc3h12a-like ribonuclease NYN domain protein, participates in lipid droplet formation in C. elegans. Homolog of REGE-1 in mammalian, REGNASE-1, is known to be involved in various processes such as cytokine mRNA destabilization, lipid droplet formation, angiogenesis and M2 macrophage polarization. Except for cytokine mRNA destabilization by 3’-UTR cleavage, the rest of three processes have been shown induced by REGNASE-1 dependent ER stress. Upon ER stress, the unfolded protein response (UPRER) that includes IRE-1 branch, ATF6 branch and PERK branch would be activated to recover ER homeostasis.
Previous study has shown that defect of lipid droplet formation in rege-1 mutation in C. elegans is due to fail in destabilizing mRNA of the transcription factor, ets-4. However, whether REGE-1 in C. elegans also participates in ER stress response as its mammalian counterparts is still unknown. Our phenotypical characterization of rege-1(tm3682) has shown defecting in lipid droplet formation as reported previously. To further understand whether REGE-1 is involved in UPRER in C. elegans, we tested UPRER alteration by monitoring transcript level of hsp-4p::gfp and endogenous hsp-4, an unfolded protein response marker proteins, between wild type and rege-1(tm3682) after tunicamycin induction. Our data has shown that more GFP intensity from hsp-4::gfp and increased hsp-4 transcripts production in rege-1(tm3682) than wild type strain, but no increases in transcript level was found in the major UPRER branch genes, xbp-1s. Moreover, our survival assay shows that rege-1(tm3682) has better fitness than wild type under tunicamycin environment. These data indicate that REGE-1 is likely a negative regulator in both stress induced UPRER and fitness. Our results will begin to shed some light on how REGE-1 regulates in ER stress response. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T06:41:32Z (GMT). No. of bitstreams: 1 ntu-107-R04448015-1.pdf: 2063003 bytes, checksum: 3bc8c74447712f2678e9b1ee6ab9fed8 (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 口試委員審定書 i
Acknowledgment ii 中文摘要 iii Abstract v Contents vii Chapter 1 Introduction 1 1.1 REGE-1 in C. elegans is homolog of Regnase-1 in mammalian. 1 1.2 The Endoplasmic reticulum unfolded protein response (UPR) pathways in C. elegans. 2 -1.2.1 Introduction of unfolded protein response (UPR) 2 -1.2.2 Inositol-requiring enzyme 1 (IRE1) branch 3 -1.2.3 Activating transcription factor 6 (ATF6) branch 5 -1.2.4 Protein kinase RNA-like endoplasmic reticulum kinase (PERK) branch 5 1.3 Effect of UPRER in lifespan and stress resistance in C. elegans. 6 1.4 Recent study of REGE-1 in C. elegans 8 1.5 Summary of introduction 9 Chapter 2 Materials and Methods 11 2.1 Strains 11 2.2 Oil-red O staining 11 2.3 Tunicamycin induction 12 2.4 Total RNA extraction 13 2.5 RT-PCR and RT-qPCR 13 2.6 Western blot 14 2.7 Fitness assay 15 Chapter 3 Results 16 3.1 REGE-1 deletion strain rege-1(tm3682) 16 3.2 Rege-1(tm3682) shows fat-loss phenotype. 18 3.3 Rege-1(tm3682) is more responsive to unfolded protein response in ER. 19 3.4 Fat-content variations have different effect on UPRER in C. elegans. 20 3.5 Better survival was found in rege-1(tm3682) under tunicamycin treatment. 21 3.6 REGE-1 is considered to play as a regulator or repressor in UPRER upon ER stress. 21 Chapter 4 Discussion 23 4.1 REGE-1 may act as a regulator in UPRER after ER stress induction. 23 4.2 Potential roles of REGE-1, ETS-4 and IIS pathway in longevity. 27 Chapter 5 Figures 30 Figure 1. Schematic of rege-1 gene in C. elegans and its mutant strain rege-1(tm3682). 30 Figure 2. Truncated rege-1 mRNA can be detected in rege-1(tm3682) by RT-qPCR and RT-PCR, but its REGE-1 in rege-1(tm3682) is not detected by newly customized antibody. 32 Figure 3. Rege-1(tm3682) also has fat-loss phenotype. 34 Figure 4. Elevated hsp-4p::gfp reporter and endogenous hsp-4 expression in rege-1(tm3682) after tunicamycin induction. 36 Figure 5. There is no alteration in xbp-1s, total xbp-1, and their ratio. 38 Figure 6. Reduced-fat-content mutant blmp-1(tm548) shows no statistically significance in both hsp-4 and xbp-1s as rege-1(tm3682). 40 Figure 7. Better survival rate was found in rege-1(tm3682) under tunicamycin treatment. 41 Figure 8. Proposed Model of REGE-1 in UPRER branches. 42 References 43 Appendix 49 | |
dc.language.iso | en | |
dc.title | REGE-1於秀麗隱桿線蟲中的特徵及其在內質網壓力中所扮演的角色 | zh_TW |
dc.title | Characterization of REGE-1 and its role of ER stress response in C. elegans | en |
dc.type | Thesis | |
dc.date.schoolyear | 106-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 莊立民(Lee-Ming Chuang),潘俊良(Chun-Liang Pan) | |
dc.subject.keyword | REGE-1,Regnase-1,內質網壓力,內質網的未折疊蛋白質反應,秀麗隱桿線蟲, | zh_TW |
dc.subject.keyword | REGE-1,Regnase-1,ER stress,UPRER,C. elegans, | en |
dc.relation.page | 49 | |
dc.identifier.doi | 10.6342/NTU201802565 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2018-08-15 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
Appears in Collections: | 分子醫學研究所 |
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