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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 朱雪萍 | zh_TW |
| dc.contributor.advisor | Hsueh-Ping Chu | en |
| dc.contributor.author | 顏建平 | zh_TW |
| dc.contributor.author | Chien-Ping Yen | en |
| dc.date.accessioned | 2025-08-21T16:54:27Z | - |
| dc.date.available | 2025-08-22 | - |
| dc.date.copyright | 2025-08-21 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-08-06 | - |
| dc.identifier.citation | Aguilera, A., and García-Muse, T. (2012). R loops: from transcription byproducts to threats to genome stability. Molecular Cell 46, 115-124. 10.1016/j.molcel.2012.04.009.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/99231 | - |
| dc.description.abstract | DNA損傷會嚴重阻礙核糖核酸聚合酶II（RNAPII）的進程，並引發轉錄阻斷性損傷，從而導致 R-loop 的累積。R-loop 是一種包含 DNA:RNA 雜合體和被置換的單鏈去氧核糖核酸的三鏈結構。持續的 R-loops 會觸發基因組不穩定並導致細胞死亡。R-loops 可以通過轉錄耦合核苷酸切除修復 (TC-NER) 因子被加工成去氧核糖核酸雙鏈斷裂。在紫外線損傷的反應中，大多數 RNA表現量會減少，但長非編碼核糖核酸的比例卻顯著增加。有趣的是，某些反義股長非編碼核糖核酸的轉錄水平上升，而鄰近的編碼基因在紫外線暴露後下調。值得注意的是，這些反義長非編碼核糖核酸基因和編碼基因是以頭對頭的方式排列的。驅動這些長非編碼核糖核酸上調的機制及其在紫外線壓力下的功能作用仍然知之甚少。在這篇研究裡，我發現紫外線損傷會導致WDR82 與核糖核酸聚合酶II 的分離，進而促進長非編碼核糖核酸的表達。此外，這一現象伴隨著紫外線誘導的長非編碼核糖核酸雙向啟動子處的 R-loop 形成。在紫外線損傷後，核糖核酸聚合酶 II的聚集會從編碼基因的啟動子轉移到了反義長非編碼核糖核酸基因的啟動子。抑制WDR82的表現後，紫外線誘導的長非編碼核糖核酸會增加。這些結果表明，紫外線損傷會在雙向啟動子處引發核糖核酸聚合酶 II的轉移，並且WDR82與核糖核酸聚合酶II 的分離是紫外線誘導的長非編碼核糖核酸表達的關鍵促進因子。 | zh_TW |
| dc.description.abstract | DNA damage can severely block RNA polymerase II (RNAPII) progression, leading to transcription-blocking lesions and the accumulation of R-loops, a triple-stranded structure containing a DNA:RNA hybrid and a displaced single-stranded DNA. Persistent R-loops trigger genome instability and lead to cell death. R-loops can be processed into DNA double-strand breaks by transcription-coupled nucleotide excision repair (TC-NER) factors. In response to UV damage, while the levels of most RNA are reduced, a substantial fraction of long non-coding RNAs (lncRNAs) are increased. Interestingly, the transcription levels of certain antisense lncRNAs are elevated, while the nearby coding genes are downregulated following exposure to UV. Notably, these antisense lncRNA genes and coding genes are arranged in a head-to-head orientation. The mechanism underlying the upregulation of these non-coding RNAs and their functions they undertake in response to UV stress remain poorly understood. This study reveals that the dissociation of WDR82 from RNAPII triggers the expression of lncRNAs upon UV damage. Moreover, this phenomenon is accompanied by R-loop formation at the bidirectional promoters of UV-induced lncRNAs. The RNAPII occupancy shifts from the promoters of coding genes to the promoters of antisense lncRNA genes upon UV damage. Furthermore, CUT&RUN-seq analysis reveals that the RNAPII-S5 occupancy at TSS is increased in lncRNA genes with bidirectional promoters upon UV stress, while the occupancy of WDR82 is lost. Depletion of WDR82 results in elevated expression of UV-induced lncRNAs, which is associated with increased R-loop accumulation. These results suggest that WDR82 suppresses the expression of UV-induced lncRNAs, and that the dissociation of WDR82 from RNAPII triggers shifts in RNAPII occupancy at bidirectional promoters, thereby promoting lncRNA expression upon UV damage. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-08-21T16:54:27Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-08-21T16:54:27Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 論文口試委員會審定書 i
誌謝 ii 中文摘要 iii Abstract v Content vii Content of Figures xii Content of Tables xiv Abbreviations xv Chapter1 Introduction 1 1.1 UV Induces DNA Damage and RNA Pol II Stalling. 1 1.2 UV Irradiation-Induced lncRNAs 3 1.3 R-Loop 4 1.4 Nascent RNAs Re-Invade to Form R-Loops in Cis 5 1.5 The Role of R-Loops in Transcription Regulation and Genome Stability 6 1.6 DNA Damages Trigger G Clusters R-Loop Formation 7 1.7 Laser Induces DNA Damage and R-Loop Formation 9 1.8 XPF 9 1.9 Resolution of R-Loops via TC-NER (Transcription-Coupled Nucleotide Excision Repair) 12 1.10 Long Non-Coding RNA-Mediated Transcriptional Regulation 13 1.11 UV Irradiation-Induced lncRNAs and R-Loops 15 1.12 The Function of UV-Induced lncRNAs in the Cell Cycle 16 1.13 Regulatory Mechanisms of lncRNA Transcription in Bidirectional Transcription Regions 17 1.14 WDR82 21 1.15 The ZWC Complex 23 1.16 Hypothesis 24 Chapter2 Materials and Methods 27 2.1 Cell Culture and UVC Treatment 27 2.2 siRNA Transfection 27 2.3 DRIP-qPCR 28 2.4 RNA Extraction 29 2.5 cDNA Synthesis 30 2.6 Western Blot 30 2.7 CUT&RUN 31 2.8 MapR 32 2.9 RNAPII pS5- WDR82 PLA (Proximity Ligation Assay) 34 2.10 Statistical Analysis for Images 35 2.11 Illumina Library Preparation for CUT&RUN and MapR 36 2.12 NGS Sequencing for CUT&RUN and MapR 36 2.13 Enrichment Analysis by Hypergeometric Test 38 Chapter3 Results 41 3.1 UV Induces Expression of lncRNAs Driven by Bidirectional Promoters 41 3.2 UV Exposure Increases RNAPII pS5 at the TSS-Proximal Region of UV-Induced lncRNAs 42 3.3 UV Induces R-Loop Formation near Transcription Start Sites 42 3.4 XPF Deficiency Dysregulates Expression of UV-Induced-lncRNAs 43 3.5 WDR82 Deficiency Triggers the Transcription of UV-Induced lncRNAs in Bidirectional Transcription Regions 44 3.6 RNAPII pS5 Occupancy is Enriched at TSS-Proximal Regions of Bidirectional Genes upon UV Damage 44 3.7 XPF Depletion Results in Reduced RNAPII pS5 Occupancy at TSS-Proximal Regions of UV-Induced RNAPII pS5 Genes 46 3.8 RNAPII pS5 Occupancy is Reduced in siWdr82 Knockdown at TSS-Proximal Regions of UV-Induced RNAPII pS5 Occupancy Genes 47 3.9 Increased RNAPII pS5 Occupancy at TSS in Response to UV Stress upon Depletion of XPF and WDR82 48 3.10 Clusters of Differential RNAPII pS5 Coverage in UV-Induced lncRNA Genes in Response to UV Damage, XPF or WDR82 Depletion 50 3.11 Increased Occupancy of UV-Induced RNAPII pS5 at the TSS-Proximal Region in XPF or WDR82 Deficient Cells 51 3.12 Elevated R-Loop Occupancy under UV Stress at the TSS Regions of Bidirectional Transcription Genes 52 3.13 Genes with Elevated R-Loop Occupancy upon XPF Depletion are Associated with Increased R-Loop Formation in Response to UV Stress 53 3.14 WDR82 Depletion Results in Elevated R-Loop Occupancy at TSS of UV-Induced R-Loop Occupancy Genes 54 3.15 Increased R-Loop Occupancy at TSS-Proximal Regions in XPF and WDR82 Deficient Cells upon UV Stress 56 3.16 Genes with Increased RNAPII pS5 Occupancy are Associated with Increased R-Loops at the TSS in Response to UV Stress 57 3.17 Clusters of Differential R-Loop Coverage in UV-Induced lncRNA Genes in Response to UV Damage, XPF or WDR82 Depletion 58 3.18 UV-Induced R-Loop Formation in the TSS-Proximal Regions is Compromised in XPF and WDR82 Deficient cells 59 3.19 WDR82 Dissociates from RNAPII pS5 upon UV Stress 59 Chapter4 Conclusion 61 Chapter5 Discussion 63 Chapter6 Supplementary information 121 Chapter7 References 132 | - |
| dc.language.iso | en | - |
| dc.subject | 紫外線 | zh_TW |
| dc.subject | 核糖核酸聚合酶II | zh_TW |
| dc.subject | 長非編碼核糖核酸 | zh_TW |
| dc.subject | R-loop | zh_TW |
| dc.subject | XPF | zh_TW |
| dc.subject | WDR82 | zh_TW |
| dc.subject | long non-coding RNA (lncRNA) | en |
| dc.subject | Ultraviolet (UV) | en |
| dc.subject | WDR82 | en |
| dc.subject | XPF | en |
| dc.subject | R-loop | en |
| dc.subject | RNA polymerase II (RNAP II) | en |
| dc.title | WDR82在紫外線損傷下調控雙向啟動子區長鏈非編碼RNA表達及R環形成的作用機制 | zh_TW |
| dc.title | WDR82-Mediated Regulation of LncRNA Expression and R-loop Formation at Bidirectional Promoters in Response to UV Damage | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-2 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.oralexamcommittee | 高承福;冀宏源;吳青錫;朱家瑩 | zh_TW |
| dc.contributor.oralexamcommittee | Cheng-Fu Kao;Peter Hung-Yuan Chi;Ching-Shyi Wu;Chia-Ying Chu | en |
| dc.subject.keyword | 紫外線,核糖核酸聚合酶II,長非編碼核糖核酸,R-loop,XPF,WDR82, | zh_TW |
| dc.subject.keyword | Ultraviolet (UV),RNA polymerase II (RNAP II),long non-coding RNA (lncRNA),R-loop,XPF,WDR82, | en |
| dc.relation.page | 144 | - |
| dc.identifier.doi | 10.6342/NTU202502996 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2025-08-09 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 基因體與系統生物學學位學程 | - |
| dc.date.embargo-lift | 2025-08-22 | - |
| 顯示於系所單位： | 基因體與系統生物學學位學程 | |
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