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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 譚婉玉 | zh_TW |
| dc.contributor.advisor | Woan-Yuh Tarn | en |
| dc.contributor.author | 楊謦潞 | zh_TW |
| dc.contributor.author | Sabrina Yeo Samuel | en |
| dc.date.accessioned | 2023-09-08T16:05:12Z | - |
| dc.date.available | 2023-11-10 | - |
| dc.date.copyright | 2023-09-08 | - |
| dc.date.issued | 2023 | - |
| dc.date.submitted | 2023-07-27 | - |
| dc.identifier.citation | Abakir, A., Giles, T. C., Cristini, A., Foster, J. M., Dai, N., Starczak, M., Li, M., Eleftheriou, M., Crutchley, J., Flatt, L., Young, L., Gaffney, D. J., Denning, C., Dalhus, B., Emes, R. D., Gackowski, D., Corrêa, I. R., Garcia -Perez, L., J., Klungland, A., Gromak, N., Ruzov, A. (2020). N6-methyladenosine regulates the stability of RNA:DNA hybrids in human cells. Nature Genetics, 52(1), 48- 55. https://doi.org/10.1038/s41588-019-0549-x
Alberti, S., Gladfelter, A. S., & Mittag, T. (2019). Considerations and Challenges in Studying Liquid-Liquid Phase Separation and Biomolecular Condensates. Cell, 176(3), 419–434. https://doi.org/10.1016/j.cell.2018.12.035 André, A. A. M., and Spruijt, E. (2020). Liquid -liquid phase separation in crowded environments. International Journal of Molecular Sciences, 21(16), 5908–5908. https://doi.org/10.3390/ijms21165908 Banani, S. F., Lee, H., Hyman, A. A., & Rosen, M. J. (2017). Biomolecular condensates: organizers of cellular biochemistry. Nature Reviews Molecular Cell Biology, 18(5), 285–298. https://doi.org/10.1038/nrm.2017.7 Bekker-Jensen, S., Lukas, C., Kitagawa, R., Melander, F., Kastan, M. B., Bartek, J., & Lukas, J. (2006). Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks. Journal of Cell Biology, 173(2), 195–206. https://doi.org/10.1083/jcb.200510130 Boehm, V., & Gehring, N. H. (2016). Exon Junction Complexes: Supervising the Gene Expression Assembly Line. Trends in Genetics, 32(11), 724–735. https://doi.org/10.1016/j.tig.2016.09.003 Chuang, T.W., Lee, K.M., Lou, Y.C., Lu, C.C., & Tarn, W.Y. (2016). A Point Mutation in the Exon Junction Complex Factor Y14 Disrupts Its Function in mRNA Cap Binding and Translation Enhancement. Journal of Biological Chemistry, 291(16), 8565-8574. https://doi.org/10.1074/jbc.M115.704544 Chuang, T.W., Lu, C.C., Su, C.H., Wu, P.Y., Sarasvathi E., Lee, C.C., Kuo, H.C., Hung, K.Y., Lee, K.M., Tsai, C.Y., & Tarn, W.Y. (2019). The RNA Processing Factor Y14 Participates in DNA Damage Response and Repair. IScience, 13, 402–415. https://doi.org/10.1016/j.isci.2019.03.005 Chen, K., Lu, Z., Wang, X., Fu, Y., Luo, Z., Liu, N., Han, D., Dominissini, D., Dai, Q., Pan, T., & He, C. (2015). High-Resolution N6-Methyladenosine (m6A) Map Using Photo-Crosslinking-Assisted m6A Sequencing. Angewandte Chemie (International ed. in English), 54(5), 1587. https://doi.org/10.1002/anie.201410647 Chuang, T.W., Su, C.H., Wu, P.Y., Chang, Y.M., & Tarn, W.Y. (2023). LncRNA HOTAIRM1 functions in DNA double-strand break repair via its association with DNA repair and mRNA surveillance factors. Nucleic Acids Research. https://doi.org/10.1093/nar/gkad143 Ciccia, A., & Elledge, S. J. (2010). The DNA Damage Response: Making It Safe to Play with Knives. Molecular Cell, 40(2), 179–204. https://doi.org/10.1016/j.molcel.2010.09.019 Diaz-Lagares, A., Crujeiras, A. B., Lopez-Serra, P., Soler, M., Setien, F., Goyal, A., Sandoval, J., Hashimoto, Y., Martínez -Cardús, A., Gomez, A., Heyn, H., Moutinho, C., Espada, J., Vidal, A., Paules M., Galán M., Sala, N., Akiyama, Y., Martínez -Iniesta M., & Farre, L. (2016) Epigenetic inactivation of the p53- induced long noncoding RNA TP53 target 1 in human cancer. Proceedings of the National Academy of Sciences, 113(47), E7535-E7544. https://doi.org/10.1073/pnas.1608585113 D’Alessandro, G., & d’Adda di Fagagna, F. (2017). Transcription and DNA Damage: Holding Hands or Crossing Swords? Journal of Molecular Biology, 429(21), 3215–3229. https://doi.org/10.1016/j.jmb.2016.11.002 Espinosa, J. R., Joseph, J. A., Sanchez-Burgos, I., Adiran Garaizar, Frenkel, D., & Collepardo-Guevara, R. (2020). Liquid network connectivity regulates the stability and composition of biomolecular condensates with many components. Proceedings of the National Academy of Sciences of the United States of America, 117(24), 13238–13247. https://doi.org/10.1073/pnas.1917569117 Fay, M. M., & Anderson, P. J. (2018). The Role of RNA in Biological Phase Separations. Journal of Molecular Biology, 430(23), 4685-4701. https://doi.org/10.1016/j.jmb.2018.05.003 Fukumura, K., Wakabayashi, S.-I., Kataoka, N., Sakamoto, H., Suzuki, Y., Nakai, K., Mayeda, A., & Inoue, K. (2016). The Exon Junction Complex Controls the Efficient and Faithful Splicing of a Subset of Transcripts Involved in Mitotic Cell-Cycle Progression. International Journal of Molecular Sciences, 17(8), 1153–1153. https://doi.org/10.3390/ijms17081153 Fung, H. Y. J., Birol, M., & Rhoades, E. (2018). IDPs in macromolecular complexes: the roles of multivalent interactions in diverse assemblies. Current Opinion in Structural Biology, 49, 36–43. https://doi.org/10.1016/j.sbi.2017.12.007 Haemmig, S., Yang, D., Sun, X., Das, D., Ghaffari, S., Molinaro, R., Chen, L., Deng, Y., Freeman, D., Moullan, N., Tesmenitsky, Y., Khyrul Wara, K. M., Simion, V., Shvartz, E., Lee, J. F., Yang, T., Sukova, G., Marto, J. A., Stone, P. H., Lee, W. L., Auwerx J., Libby P., Feinberg, M. W. (2020). Long noncoding RNA SNHG12 integrates a DNA-PK–mediated DNA damage response and vascular senescence. Science Translational Medicine. https://doi.org/aaw1868 Hawley, B. R., Lu, W., Wilczynska, A., & Bushell, M. (2017). The emerging role of RNAs in DNA damage repair. Cell Death & Differentiation, 24(4), 580-587. https://doi.org/10.1038/cdd.2017.16 Hingorani, K., Attila Szebeni, & Olson, M. E. (2000). Mapping the Functional Domains of Nucleolar Protein B23. 275(32), 24451–24457. https://doi.org/10.1074/jbc.m003278200 Holehouse, A. S., Das, R. K., Ahad, J. N., Richardson, M. O., & Pappu, R. V. (2017). CIDER: Resources to Analyze Sequence-Ensemble Relationships of Intrinsically Disordered Proteins. Biophysical Journal, 112(1), 16-21. https://doi.org/10.1016/j.bpj.2016.11.3200 Hyman, A. A., Weber, C. A. & Jülicher, F. (2014) Liquid-Liquid Phase Separation in Biology Annual Review of Cell and Developmental Biology 30, 39–58. https://doi.org/10.1146/annurev-cellbio-100913-013325 Kai, M. (2016). Roles of RNA-Binding Proteins in DNA Damage Response. International Journal of Molecular Sciences, 17(3). https://doi.org/10.3390/ijms17030310 Langdon, E. M., Qiu, Y., Niaki, A. G., McLaughlin, G. A., Weidmann, C. A., Gerbich, T. M., Smith, J. A., Crutchley, J. M., Termini, C. M., Weeks, K. M., Myong, S., & Gladfelter, A. S. (2018). mRNA structure determines specificity of a polyQ- driven phase separation. Science, 360(6391), 922-927 https://doi.org/10.1126/science.aar7432 Lee, H. G., Kim, J., & Seo, P. J. (2022). N6-methyladenosine–modified RNA acts as a molecular glue that drives liquid–liquid phase separation in plants. Plant Signaling & Behavior, 17(1). https://doi.org/10.1080/15592324.2022.2079308 Levone, B. R., Lenzken, S. C., Antonaci, M., Maiser, A., Rapp, A., Conte, F., Reber, S., Mechtersheimer, J., Ronchi, A. E., Mühlemann, O., Leonhardt, H., Cardoso, M. C., Ruepp, M.-D., & Barabino, S. M. L. (2021). FUS-dependent liquid–liquid phase separation is important for DNA repair initiation. Journal of Cell Biology, 220(5). https://doi.org/10.1083/jcb.202008030 Li, Q., Peng, X., Li, Y., Tang, W., Zhu, J., Huang, J., Qi, Y., & Zhang, Z. (2020). LLPSDB: A database of proteins undergoing liquid–liquid phase separation in vitro. Nucleic Acids Research, 48(D1), D320-D327. https://doi.org/10.1093/nar/gkz778 Lin, Y., Protter, D. S., Rosen, M. K., & Parker, R. (2015). Formation and Maturation of Phase-Separated Liquid Droplets by RNA-Binding Proteins. Molecular Cell, 60(2), 208-219. https://doi.org/10.1016/j.molcel.2015.08.018 Lisby, M., Barlow, J. H., Burgess, R. C., & Rothstein, R. (2004). Choreography of the DNA Damage Response. Cell, 118(6), 699–713. https://doi.org/10.1016/j.cell.2004.08.015 Lu, C.-C., Lee, C.-C., Tseng, C.-T., & Tarn, W.-Y. (2017). Y14 governs p53 expression and modulates DNA damage sensitivity. Scientific Reports, 7(1). https://doi.org/10.1038/srep45558 Maharana, S., Wang, J., Papadopoulos, D. K., Richter, D., Pozniakovsky, A., Poser, I., Bickle, M., Rizk, S., Guillén -Boixet, J., Franzmann, T. M., Jahnel, M., Marrone, L., Chang, T., Sterneckert, J., Tomancak, P., Hyman, A. A., & Alberti, S. (2018). RNA buffers the phase separation behavior of prion-like RNA binding proteins. Science, 360, 918-921. https://doi.org/10.1126/science.aar7366 Meng, X., Yang, S., & Camp, V. J. A. (2020). The Interplay Between the DNA Damage Response, RNA Processing and Extracellular Vesicles. Frontiers in Oncology, 9. https://doi.org/10.3389/fonc.2019.01538 Michelle, L., Cloutier, A., Toutant, J., Lulzim Shkreta, Thibault, P., Durand, M., Garneau, D., Gendron, D., Lapointe, E., Couture, S., Hervé Le Hir, Klinck, R., Sherif Abou Elela, Panagiotis Prinos, & Chabot, B. (2012). Proteins Associated with the Exon Junction Complex Also Control the Alternative Splicing of Apoptotic Regulators. Molecular and Cellular Biology, 32(5), 954–967. https://doi.org/10.1128/mcb.06130-11 Michelini, F., Pitchiaya, S., Vitelli, V., Sharma, S., Gioia, U., Pessina, F., Cabrini, M., Wang, Y., Capozzo, I., Iannelli, F., Matti, V., Francia, S., Shivashankar, G. V., & Walter, N. G. (2017). Damage-induced lncRNAs control the DNA damage response through interaction with DDRNAs at individual double-strand breaks. Nature cell biology, 19(12), 1400. https://doi.org/10.1038/ncb3643 Navarro, M. G., Kashida, S., Chouaib, R., Souquere, S., Pierron, G., Weil, D., & Gueroui, Z. (2019). RNA is a critical element for the sizing and the composition of phase-separated RNA–protein condensates. Nature Communications, 10(1), 1-13. https://doi.org/10.1038/s41467-019-11241-6 Qu, F., Tsegay, P. S., & Liu, Y. (2021). N6-Methyladenosine, DNA Repair, and Genome Stability. Frontiers in Molecular Biosciences, 8, 645823. https://doi.org/10.3389/fmolb.2021.645823 Ray Chaudhuri, A., & Nussenzweig, A. (2017). The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nature Reviews Molecular Cell Biology, 18(10), 610-621. https://doi.org/10.1038/nrm.2017.53 Sharma, V., Khurana, S., Kubben, N., Abdelmohsen, K., Oberdoerffer, P., Gorospe, M., & Misteli, T. (2015). A BRCA1-interacting lncRNA regulates homologous recombination. EMBO Reports, 16(11), 1520-1534. https://doi.org/10.15252/embr.201540437 Sukhanova, M. V., Singatulina, A. S., Pastré, D., & Lavrik, O. I. (2020). Fused in Sarcoma (FUS) in DNA Repair: Tango with Poly(ADP-ribose) Polymerase 1 and Compartmentalisation of Damaged DNA. International Journal of Molecular Sciences, 21(19). https://doi.org/10.3390/ijms21197020 Wang, J., Choi, J. M., Holehouse, A. S., Lee, H. O., Zhang, X., Jahnel, M., et al. (2018). A molecular grammar governing the driving forces for phase separation of prion- like RNA binding proteins. Cell 174, 688–699. https://doi.org/10.1016/j.cell.2018.06.006 Wang, J., Wang, L., Diao, J., Shi, Y. G., Shi, Y., Ma, H., & Shen, H. (2020). Binding to m6A RNA promotes YTHDF2-mediated phase separation. Protein & Cell, 11(4), 304-307. https://doi.org/10.1007/s13238-019-00660-2 Whelan, D. R., Howard, S. M., Vitelli, V., Renaudin, X., Adamowicz, M., Iannelli, F., Winston, C., Lee, M., Matti, V., Lee, W. T., Morten, M. J., Venkitaraman, A. R., Cejka, P., & Rothenberg, E. (2018). BRCA2 controls DNA:RNA hybrid level at DSBs by mediating RNase H2 recruitment. Nature Communications, 9(1), 1-17. https://doi.org/10.1038/s41467-018-07799-2 Van Treeck, B., Protter, D. S., Matheny, T., Khong, A., Link, C. D., & Parker, R. (2018). RNA self-assembly contributes to stress granule formation and defining the stress granule transcriptome. Proceedings of the National Academy of Sciences, 115(11), 2734-2739. https://doi.org/10.1073/pnas.1800038115 Vohhodina, J., Barros, E. M., Savage, A. L., Liberante, F. G., Manti, L., Bankhead, P., Cosgrove, N., Madden, A. F., Harkin, D. P., & Savage, K. I. (2017). The RNA processing factors THRAP3 and BCLAF1 promote the DNA damage response through selective mRNA splicing and nuclear export. Nucleic Acids Research, 45(22), 12816-12833. https://doi.org/10.1093/nar/gkx1046 Yu, C.L., Chuang, T.W., Samuel, S. Y., Lou, Y.C., & Tarn, W.Y. (2023). Co-phase separation of Y14 and RNA in vitro and its implication for DNA repair. RNA, rna.079514.122. https://doi.org/10.1261/rna.079514.122 | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/89508 | - |
| dc.description.abstract | none | zh_TW |
| dc.description.abstract | Y14 is a multifunctional RNA processing factor that plays an essential role in RNA metabolism and also participates in non-homologous end joining (NHEJ)-mediated repair of DNA double-strand breaks (DSBs). Our recent study has uncovered a long non-coding RNA (lncRNA) HOTAIRM1 that mediates the interaction between Y14 and the NHEJ factors. In this study, I first examined the molecular interaction between Y14 and RNA, in particular, HOTAIRM1. RNA electrophoretic mobility shift assay (REMSA) revealed that Y14 bound to multiple regions of HOTAIRM1. Our recent study also revealed that Y14 has the capability to undergo liquid-liquid phase separation (LLPS), and can co-phase-separate with HOTAIRM1. Therefore, I evaluated whether RNA structure or modification affects the LLPS properties of Y14. Moreover, since DNA damage induced m6A modification of HOTAIRM1, I also evaluated whether RNA methylation also affects the LLPS of Y14. My apparent data revealed that methylation enhanced Y14 LLPS. Since LLPS may involve electrostatic interactions of intrinsically disordered domains, I evaluated whether specific charge patterns can modulate a protein’s LLPS capacity. The multifunctionality of Y14 and its biochemical properties make it a valuable target for further research in understanding its role in RNA metabolism and DSB repair. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-09-08T16:05:12Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2023-09-08T16:05:12Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | Table of Contents
Acknowledgements i Abstract ii Table of Contents iii List of Figures/Appendixes v Introduction 1. Liquid-liquid phase separation 1 2. Phase separation regulates DNA repair 3 3. Role of RNA and RNA processing factors in DNA damage repair 4 4. Y14 is an RNA processing factor involved in DNA damage repair 5 Results 1. RNA binding analysis of recombinant human Y14 protein 7 2. Characterization of Y14 LLPS 8 3. Different RNAs modulate Y14 LLPS differently 9 4. RNA methylation promotes Y14 LLPS 10 5. Bioinformatics analysis of charged IDRs in RNA processing and DNA repair factors 11 Discussion 14 Experimental Procedures 16 References 21 Figures 29 Appendixes 41 | - |
| dc.language.iso | en | - |
| dc.subject | none | zh_TW |
| dc.subject | Liquid-liquid phase separation | en |
| dc.subject | Electrostatic interaction | en |
| dc.subject | N6-methyladenosine modification | en |
| dc.subject | DNA damage repair | en |
| dc.subject | RNA processing factor | en |
| dc.subject | Intrinsically disordered domain | en |
| dc.title | Studying Y14-RNA interaction and co-phase separation | zh_TW |
| dc.title | Studying Y14-RNA interaction and co-phase separation | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 111-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 吳惠南;蔡欣祐;蔡松智 | zh_TW |
| dc.contributor.oralexamcommittee | Huey-Nan Wu;Hsin-Yue Tsai;Kevin Tsai | en |
| dc.subject.keyword | none, | zh_TW |
| dc.subject.keyword | Liquid-liquid phase separation,Electrostatic interaction,RNA processing factor,DNA damage repair,N6-methyladenosine modification,Intrinsically disordered domain, | en |
| dc.relation.page | 50 | - |
| dc.identifier.doi | 10.6342/NTU202302064 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2023-07-27 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 分子醫學研究所 | - |
| 顯示於系所單位： | 分子醫學研究所 | |
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