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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 詹世鵬(Shih-Peng Chan) | |
| dc.contributor.author | Jei-Sheng Chang | en |
| dc.contributor.author | 張傑盛 | zh_TW |
| dc.date.accessioned | 2021-07-11T15:10:08Z | - |
| dc.date.available | 2024-08-07 | |
| dc.date.copyright | 2019-08-29 | |
| dc.date.issued | 2019 | |
| dc.date.submitted | 2019-08-09 | |
| dc.identifier.citation | Aeschimann, F., Kumari, P., Bartake, H., Gaidatzis, D., Xu, L., Ciosk, R., and Grosshans, H. (2017). LIN41 Post-transcriptionally Silences mRNAs by Two Distinct and Position-Dependent Mechanisms. Mol Cell 65, 476-+.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78655 | - |
| dc.description.abstract | The let-7 microRNA is an evolutionarily conserved microRNA that down regulates gene expression by co-operating with RNA induced silencing complex (RISC). In C. elegans, the let-7 miRNA starts to express at the larva 3 (L3) stage of and continuously accumulates through the L4 stage, leading to cell differentiation that is crucial to the L4-to-adult transition. Mutations in let-7 results in developmental phenotypes, such as vulva bursting and the abnormality of seam cell proliferation and differentiation. Previously, by RNAi screening, we found that depleting an RNA binding protein, hrp-2, suppressed phenotypes of hypomorphic and temperature-sensitive let-7(n2853) mutant allele, which contains a G-to-A point mutation at the let-7 seed region sequence. let-7 miRNA regulates C. elegans L4/adult transition by targeting lin-41 3' UTR. Down regulation of lin-41 allows expression of genes for C. elegans maturation. This regulation has been demonstrated to be an evolutionarily conserved pathway from the nematode to human, in which TRIM71, the lin-41 homolog, is regulated by human let-7 miRNA. Here, we knocked down hnRNP Q, the hrp-2 homolog, expression in human hepatocellular carcinoma cells and, interestingly detected decreased expression of TRIM7, the human homolog of lin-41, and Lin28B, the negative regulator of let-7 biogenesis. We found that the let-7 miRNA levels increased in hnRNP Q depleted HuH7 cells, as well as HEK293T cells, which may link to reduced activity of lin41 3' UTR luciferase reporter. Expressing RNAi-resistant hnRNP Q vectors in those cells partially restores effects of hnRNP Q depletion. Although the mechanism underlying for hnRNP Q modulating the let-7/TRIM71 regulation and LIN28B expression remains unclear, our findings indicate that hnRNP Q may regulate the let-7/TRIM71 pathway by affecting let-7 miRNA biogenesis. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:10:08Z (GMT). No. of bitstreams: 1 ntu-108-R06445127-1.pdf: 6459846 bytes, checksum: bcb241fc5892baccfba789f78a840c55 (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 國立臺灣大學（碩）博士學位論文口試委員會審定書 I
誌謝 II 中文摘要 III ABSTRACT V CONTENTS VII Introduction 1 The evolutionarily conserved miRNA, let-7, regulates important development-regulating genes of C. elegans also controlling disease progression in human. 1 Tripartite motif 71 (TRIM71) regulates translation by targeting to 5' or 3' UTR of target mRNAs. 2 LIN28 sustains stemness by repressing the biogenesis of let-7 miRNA and promoting proliferation of iPSC. 4 Studies in seam cell differentiation are valuable at the field of cell reprogramming. 5 The heterogeneous nuclear ribonucleoprotein Q (hnRNP Q) regulates mRNA metabolism and is related to several diseases. 6 Project aim—To investigate the role of hnRNP Q in the let-7/TRIM71 pathway. 7 Materials and methods 9 Cell culture and Transfection 9 RNA interference (RNAi) 10 Western blotting 12 Northern Blotting 15 Luciferase assay 17 Plasmid construction 19 Results 21 hnRNP Q depletion decreased the protein levels of TRIM71 and LIN28B in HuH7 cells. 21 hnRNP Q depletion increased the expression levels of let-7 miRNA. 21 hnRNP Q depletion decreased the luciferase activities of LIN41 3' UTR bearing renilla luciferase. 22 Overexpressing HA tagged hnRNP Qr06 suppressed effects of sh_hnRNP Q06 mediated RNAi. 24 Discussion 25 Modulating the homeostasis of hnRNPs might finetune cell fate. 25 hnRNP Q might regulate let-7 miRNA biosynthesis through LIN28 dependent or independent pathway. 26 Figures 28 Figure 1. hnRNP Q depletion downregulated TRIM71 and LIN28B in HuH7 cells. 28 Figure 2. hnRNP Q depletion increased let-7 miRNA levels in HuH7 cells. 29 Figure 3. hnRNP Q depletion downregulated luciferase activities of TRIM71 3' UTR bearing renilla luciferase in psiCHECK2 system. 30 Figure 4. hnRNP Q depletion did not affect the activities of TRIM71 3' UTR bearing luciferase. 32 Figure 5. Overexpressing hnRNP Qr06-3HA suppressed effects of sh_hnRNP Q06 mediated RNAi. 34 References 35 Appendix 38 Postscript 49 | |
| dc.language.iso | en | |
| dc.subject | TRIM71 | zh_TW |
| dc.subject | let-7微小核糖核酸 | zh_TW |
| dc.subject | 三端非轉譯區 | zh_TW |
| dc.subject | 異質性核糖核酸蛋白 | zh_TW |
| dc.subject | LIN28 | zh_TW |
| dc.subject | TRIM71 | en |
| dc.subject | let-7 miRNA | en |
| dc.subject | heterogeneous nuclear ribonucleoprotein | en |
| dc.subject | LIN28B | en |
| dc.title | 研究異質性核糖核酸蛋白Q
在let-7/TRIM71路徑中所扮演的角色 | zh_TW |
| dc.title | To investigate the role of heterogeneous nuclear ribonucleoprotein Q in let-7/TRIM71 pathway | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 107-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 顏伯勳(BO-SHIUN YAN),陳建源(Chien-Yuan-Chen) | |
| dc.subject.keyword | let-7微小核糖核酸,三端非轉譯區,異質性核糖核酸蛋白,TRIM71,LIN28, | zh_TW |
| dc.subject.keyword | let-7 miRNA,heterogeneous nuclear ribonucleoprotein,TRIM71,LIN28B, | en |
| dc.relation.page | 50 | |
| dc.identifier.doi | 10.6342/NTU201902591 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2019-08-12 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 微生物學研究所 | zh_TW |
| dc.date.embargo-lift | 2024-08-07 | - |
| 顯示於系所單位： | 微生物學科所 | |
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