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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 張典顯(Tien-Hsien Chang) | |
dc.contributor.author | Chia-Jui Liu | en |
dc.contributor.author | 劉家睿 | zh_TW |
dc.date.accessioned | 2021-06-15T16:15:52Z | - |
dc.date.available | 2020-08-24 | |
dc.date.copyright | 2020-08-24 | |
dc.date.issued | 2020 | |
dc.date.submitted | 2020-08-07 | |
dc.identifier.citation | Ashwal-Fluss, R., Meyer, M., Pamudurti, N. R., Ivanov, A., Bartok, O., Hanan, M., . . . Kadener, S. (2014). circRNA biogenesis competes with pre-mRNA splicing. Mol Cell, 56(1), 55-66. doi:10.1016/j.molcel.2014.08.019 Bachmayr-Heyda, A., Reiner, A. T., Auer, K., Sukhbaatar, N., Aust, S., Bachleitner-Hofmann, T., . . . Pils, D. (2015). Correlation of circular RNA abundance with proliferation--exemplified with colorectal and ovarian cancer, idiopathic lung fibrosis, and normal human tissues. Sci Rep, 5, 8057. doi:10.1038/srep08057 Bahn, J. H., Zhang, Q., Li, F., Chan, T. M., Lin, X., Kim, Y., . . . Xiao, X. (2015). The landscape of microRNA, Piwi-interacting RNA, and circular RNA in human saliva. Clin Chem, 61(1), 221-230. doi:10.1373/clinchem.2014.230433 Black, D. L. (2003). Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem, 72, 291-336. doi:10.1146/annurev.biochem.72.121801.161720 Boeckel, J. N., Jaé, N., Heumüller, A. W., Chen, W., Boon, R. A., Stellos, K., . . . Dimmeler, S. (2015). Identification and Characterization of Hypoxia-Regulated Endothelial Circular RNA. Circ Res, 117(10), 884-890. doi:10.1161/circresaha.115.306319 Burd, C. E., Jeck, W. R., Liu, Y., Sanoff, H. K., Wang, Z., Sharpless, N. E. (2010). Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk. PLoS Genet, 6(12), e1001233. doi:10.1371/journal.pgen.1001233 Cherry, J. M., Hong, E. L., Amundsen, C., Balakrishnan, R., Binkley, G., Chan, E. T., . . . Wong, E. D. (2012). Saccharomyces Genome Database: the genomics resource of budding yeast. Nucleic Acids Res, 40(Database issue), D700-705. doi:10.1093/nar/gkr1029 Chuang, T. J., Wu, C. S., Chen, C. Y., Hung, L. Y., Chiang, T. W., Yang, M. Y. (2016). NCLscan: accurate identification of non-co-linear transcripts (fusion, trans-splicing and circular RNA) with a good balance between sensitivity and precision. Nucleic Acids Res, 44(3), e29. doi:10.1093/nar/gkv1013 Conn, S. J., Pillman, K. A., Toubia, J., Conn, V. M., Salmanidis, M., Phillips, C. A., . . . Goodall, G. J. (2015). The RNA binding protein quaking regulates formation of circRNAs. Cell, 160(6), 1125-1134. doi:10.1016/j.cell.2015.02.014 Conn, V. M., Hugouvieux, V., Nayak, A., Conos, S. A., Capovilla, G., Cildir, G., . . . Conn, S. J. (2017). A circRNA from SEPALLATA3 regulates splicing of its cognate mRNA through R-loop formation. Nat Plants, 3, 17053. doi:10.1038/nplants.2017.53 Crick, F. (1970). Central dogma of molecular biology. Nature, 227(5258), 561-563. doi:10.1038/227561a0 Djebali, S., Davis, C. A., Merkel, A., Dobin, A., Lassmann, T., Mortazavi, A., . . . Gingeras, T. R. (2012). Landscape of transcription in human cells. Nature, 489(7414), 101-108. doi:10.1038/nature11233 Du, W. W., Yang, W., Chen, Y., Wu, Z. K., Foster, F. S., Yang, Z., . . . Yang, B. B. (2017). Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses. Eur Heart J, 38(18), 1402-1412. doi:10.1093/eurheartj/ehw001 Du, W. W., Yang, W., Liu, E., Yang, Z., Dhaliwal, P., Yang, B. B. (2016). Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2. Nucleic Acids Res, 44(6), 2846-2858. doi:10.1093/nar/gkw027 Fischer, J. W., Busa, V. F., Shao, Y., Leung, A. K. L. (2020). Structure-Mediated RNA Decay by UPF1 and G3BP1. Mol Cell, 78(1), 70-84.e76. doi:10.1016/j.molcel.2020.01.021 Gao, Y., Wang, J., Zhao, F. (2015). CIRI: an efficient and unbiased algorithm for de novo circular RNA identification. Genome Biol, 16(1), 4. doi:10.1186/s13059-014-0571-3 Guo, J. U., Agarwal, V., Guo, H., Bartel, D. P. (2014). Expanded identification and characterization of mammalian circular RNAs. Genome Biol, 15(7), 409. doi:10.1186/s13059-014-0409-z Hansen, T. B., Jensen, T. I., Clausen, B. H., Bramsen, J. B., Finsen, B., Damgaard, C. K., Kjems, J. (2013). Natural RNA circles function as efficient microRNA sponges. Nature, 495(7441), 384-388. doi:10.1038/nature11993 Hansen, T. B., Kjems, J., Damgaard, C. K. (2013). Circular RNA and miR-7 in cancer. Cancer Res, 73(18), 5609-5612. doi:10.1158/0008-5472.Can-13-1568 Hansen, T. B., Venø, M. T., Damgaard, C. K., Kjems, J. (2016). Comparison of circular RNA prediction tools. Nucleic Acids Res, 44(6), e58. doi:10.1093/nar/gkv1458 Hansen, T. B., Wiklund, E. D., Bramsen, J. B., Villadsen, S. B., Statham, A. L., Clark, S. J., Kjems, J. (2011). miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA. Embo j, 30(21), 4414-4422. doi:10.1038/emboj.2011.359 Houseley, J. M., Garcia-Casado, Z., Pascual, M., Paricio, N., O'Dell, K. M., Monckton, D. G., Artero, R. D. (2006). Noncanonical RNAs from transcripts of the Drosophila muscleblind gene. J Hered, 97(3), 253-260. doi:10.1093/jhered/esj037 Ivanov, A., Memczak, S., Wyler, E., Torti, F., Porath, H. T., Orejuela, M. R., . . . Rajewsky, N. (2015). Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Rep, 10(2), 170-177. doi:10.1016/j.celrep.2014.12.019 Jeck, W. R., Sharpless, N. E. (2014). Detecting and characterizing circular RNAs. Nat Biotechnol, 32(5), 453-461. doi:10.1038/nbt.2890 Jeck, W. R., Sorrentino, J. A., Wang, K., Slevin, M. K., Burd, C. E., Liu, J., . . . Sharpless, N. E. (2013). Circular RNAs are abundant, conserved, and associated with ALU repeats. Rna, 19(2), 141-157. doi:10.1261/rna.035667.112 Kelly, S., Greenman, C., Cook, P. R., Papantonis, A. (2015). Exon Skipping Is Correlated with Exon Circularization. J Mol Biol, 427(15), 2414-2417. doi:10.1016/j.jmb.2015.02.018 Li, H., Durbin, R. (2010). Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics, 26(5), 589-595. doi:10.1093/bioinformatics/btp698 Li, X., Yang, L., Chen, L. L. (2018). The Biogenesis, Functions, and Challenges of Circular RNAs. Mol Cell, 71(3), 428-442. doi:10.1016/j.molcel.2018.06.034 Li, X. F., Lytton, J. (1999). A circularized sodium-calcium exchanger exon 2 transcript. J Biol Chem, 274(12), 8153-8160. doi:10.1074/jbc.274.12.8153 Li, Y., Zheng, Q., Bao, C., Li, S., Guo, W., Zhao, J., . . . Huang, S. (2015). Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res, 25(8), 981-984. doi:10.1038/cr.2015.82 Li, Z., Huang, C., Bao, C., Chen, L., Lin, M., Wang, X., . . . Shan, G. (2015). Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol, 22(3), 256-264. doi:10.1038/nsmb.2959 Liu, C. X., Li, X., Nan, F., Jiang, S., Gao, X., Guo, S. K., . . . Chen, L. L. (2019). Structure and Degradation of Circular RNAs Regulate PKR Activation in Innate Immunity. Cell, 177(4), 865-880.e821. doi:10.1016/j.cell.2019.03.046 Lopez, P. J., Séraphin, B. (1999). Genomic-scale quantitative analysis of yeast pre-mRNA splicing: implications for splice-site recognition. Rna, 5(9), 1135-1137. doi:10.1017/s135583829999091x Lu, T., Cui, L., Zhou, Y., Zhu, C., Fan, D., Gong, H., . . . Han, B. (2015). Transcriptome-wide investigation of circular RNAs in rice. Rna, 21(12), 2076-2087. doi:10.1261/rna.052282.115 Memczak, S., Jens, M., Elefsinioti, A., Torti, F., Krueger, J., Rybak, A., . . . Rajewsky, N. (2013). Circular RNAs are a large class of animal RNAs with regulatory potency. Nature, 495(7441), 333-338. doi:10.1038/nature11928 Memczak, S., Papavasileiou, P., Peters, O., Rajewsky, N. (2015). Identification and Characterization of Circular RNAs As a New Class of Putative Biomarkers in Human Blood. PLoS One, 10(10), e0141214. doi:10.1371/journal.pone.0141214 Mortazavi, A., Williams, B. A., McCue, K., Schaeffer, L., Wold, B. (2008). Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods, 5(7), 621-628. doi:10.1038/nmeth.1226 Nigro, J. M., Cho, K. R., Fearon, E. R., Kern, S. E., Ruppert, J. M., Oliner, J. D., . . . Vogelstein, B. (1991). Scrambled exons. Cell, 64(3), 607-613. doi:10.1016/0092-8674(91)90244-s Palazzo, A. F., Lee, E. S. (2015). Non-coding RNA: what is functional and what is junk? Front Genet, 6, 2. doi:10.3389/fgene.2015.00002 Park, O. H., Ha, H., Lee, Y., Boo, S. H., Kwon, D. H., Song, H. K., Kim, Y. K. (2019). Endoribonucleolytic Cleavage of m(6)A-Containing RNAs by RNase P/MRP Complex. Mol Cell, 74(3), 494-507.e498. doi:10.1016/j.molcel.2019.02.034 Rybak-Wolf, A., Stottmeister, C., Glažar, P., Jens, M., Pino, N., Giusti, S., . . . Rajewsky, N. (2015). Circular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed. Mol Cell, 58(5), 870-885. doi:10.1016/j.molcel.2015.03.027 Salzman, J., Gawad, C., Wang, P. L., Lacayo, N., Brown, P. O. (2012). Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS One, 7(2), e30733. doi:10.1371/journal.pone.0030733 Sanger, H. L., Klotz, G., Riesner, D., Gross, H. J., Kleinschmidt, A. K. (1976). Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc Natl Acad Sci U S A, 73(11), 3852-3856. doi:10.1073/pnas.73.11.3852 Spingola, M., Grate, L., Haussler, D., Ares, M., Jr. (1999). Genome-wide bioinformatic and molecular analysis of introns in Saccharomyces cerevisiae. Rna, 5(2), 221-234. doi:10.1017/s1355838299981682 Szabo, L., Salzman, J. (2016). Detecting circular RNAs: bioinformatic and experimental challenges. Nat Rev Genet, 17(11), 679-692. doi:10.1038/nrg.2016.114 Taymaz-Nikerel, H., Cankorur-Cetinkaya, A., Kirdar, B. (2016). Genome-Wide Transcriptional Response of Saccharomyces cerevisiae to Stress-Induced Perturbations. Front Bioeng Biotechnol, 4, 17. doi:10.3389/fbioe.2016.00017 Vincent, H. A., Deutscher, M. P. (2006). Substrate recognition and catalysis by the exoribonuclease RNase R. J Biol Chem, 281(40), 29769-29775. doi:10.1074/jbc.M606744200 Wang, P. L., Bao, Y., Yee, M. C., Barrett, S. P., Hogan, G. J., Olsen, M. N., . . . Salzman, J. (2014). Circular RNA is expressed across the eukaryotic tree of life. PLoS One, 9(6), e90859. doi:10.1371/journal.pone.0090859 Wang, Z., Gerstein, M., Snyder, M. (2009). RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet, 10(1), 57-63. doi:10.1038/nrg2484 Westholm, J. O., Miura, P., Olson, S., Shenker, S., Joseph, B., Sanfilippo, P., . . . Lai, E. C. (2014). Genome-wide analysis of drosophila circular RNAs reveals their structural and sequence properties and age-dependent neural accumulation. Cell Rep, 9(5), 1966-1980. doi:10.1016/j.celrep.2014.10.062 Ye, C. Y., Chen, L., Liu, C., Zhu, Q. H., Fan, L. (2015). Widespread noncoding circular RNAs in plants. New Phytol, 208(1), 88-95. doi:10.1111/nph.13585 Zaphiropoulos, P. G. (1997). Exon skipping and circular RNA formation in transcripts of the human cytochrome P-450 2C18 gene in epidermis and of the rat androgen binding protein gene in testis. Mol Cell Biol, 17(6), 2985-2993. doi:10.1128/mcb.17.6.2985 Zeng, X., Lin, W., Guo, M., Zou, Q. (2017). A comprehensive overview and evaluation of circular RNA detection tools. PLoS Comput Biol, 13(6), e1005420. doi:10.1371/journal.pcbi.1005420 Zhang, X. O., Wang, H. B., Zhang, Y., Lu, X., Chen, L. L., Yang, L. (2014). Complementary sequence-mediated exon circularization. Cell, 159(1), 134-147. doi:10.1016/j.cell.2014.09.001 Zhang, Y., Xue, W., Li, X., Zhang, J., Chen, S., Zhang, J. L., . . . Chen, L. L. (2016). The Biogenesis of Nascent Circular RNAs. Cell Rep, 15(3), 611-624. doi:10.1016/j.celrep.2016.03.058 Zhang, Y., Yang, L., Chen, L. L. (2016). Characterization of Circular RNAs. Methods Mol Biol, 1402, 215-227. doi:10.1007/978-1-4939-3378-5_17 Zhang, Y., Zhang, X. O., Chen, T., Xiang, J. F., Yin, Q. F., Xing, Y. H., . . . Chen, L. L. (2013). Circular intronic long noncoding RNAs. Mol Cell, 51(6), 792-806. doi:10.1016/j.molcel.2013.08.017 Zhao, X., Duan, X., Fu, J., Shao, Y., Zhang, W., Guo, M., Li, C. (2019). Genome-Wide Identification of Circular RNAs Revealed the Dominant Intergenic Region Circularization Model in Apostichopus japonicus. Front Genet, 10, 603. doi:10.3389/fgene.2019.00603 Zuo, J., Wang, Q., Zhu, B., Luo, Y., Gao, L. (2016). Deciphering the roles of circRNAs on chilling injury in tomato. Biochem Biophys Res Commun, 479(2), 132-138. doi:10.1016/j.bbrc.2016.07.032 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/52476 | - |
dc.description.abstract | 隨著對轉錄體的了解與研究,許多不會轉譯出蛋白質的非編碼核糖核酸逐漸被發現,其中包含了環形核糖核酸(circular RNAs, circRNAs)。基因從DNA經轉錄(transcription)形成pre-RNA後,會被剪接(splicing)成線型的RNA。然而circRNAs 的生成是透過反式剪接(back-splicing)形成環狀構造。因為其封閉環狀的構造,RNA外切酶無法有效地作用,因此這類的RNA在細胞內相對穩定且不易被降解。circRNAs最早在1976年於植物的類病毒中發現,隨著定序技術與生物資訊分析的方法的進步,在許多物種都有發現circRNAs,包括了人類、植物以及真菌。circRNAs已知的功能如下:可作為miRNA或RNA-binding protein sponge、調控基因轉錄、參與細胞應對壓力反應的調控。然而因為circRNAs的構型特殊且表現量較少,在高等真核生物中研究circRNAs 的功能仍然相當困難。因此我的目標是在透過研究酵母菌(Saccharomyces cerevisiae)中的circRNAs,進一步了解他們的功能。 酵母菌中有10個基因擁有兩個Intron,先前的研究針對這十個基因進行驗證,並報導了其中六個基因會生成circRNAs。為了更全面的探討酵母菌的circRNAs,我利用核糖核酸測序(RNA-seq)研究酵母菌circRNAs,使用偵測程式進行circRNAs的搜尋,包括了CIRI、find_circ以及NCLscan,並輔以針對性的back-splicing 序列模板進行比對,用於驗證酵母菌的circRNAs。分析指出circEFM5是酵母菌中表現最多的circRNAs,為了進一步了解circRNAs的在壓力調控中的功能,我將酵母菌培養在一系列的壓力環境中,包含了生長至靜止期(Stationary phase)、溫度變化、高濃度的鹽類、金屬離子、氧化逆境,以及缺乏氮的環境,並觀察circEFM5與其直線型RNA在細胞內的比例變化。透過RT-qPCR的結果可以觀察到EFM5環形線型的比例在不同的逆境下有所改變,暗示著circEFM5 可能會參與酵母菌的壓力反應調控。在未來希望能透過全面性分析酵母菌的circRNAs、探討其在壓力環境下的轉錄體,進而了解circRNAs的分子功能與在調控壓力反應中所扮演的角色。 | zh_TW |
dc.description.abstract | CircRNAs is a unique class of non-coding RNA revealed from explosion of transcriptomic analyses. Viroid was the first circRNA discovered in 1976. With the advance of sequencing and bioinformatic analysis, more circRNAs were identified across species, from fungi, plant to human. Different from canonical splicing, CircRNA is generated through back-splicing, in which the downstream splice site of an exon is joined to its upstream splice site. This ultimately forms a closed loop structure with 3' to 5' at the junction. CircRNAs can function as miRNA sponge, regulation of transcription and involving in stress responses. However, the functional study of circRNA remains highly challenging in higher eukaryotes because of its unique structure, low abundancy, I aimed to address this issue by studying circRNAs in the budding yeast (Saccharomyces cerevisiae), which is a powerful and well-established model system. Previously, ten genes in yeast with two introns were surveyed and six of them were found to produce circRNAs. To investigate yeast circRNAs in a more comprehensive way, I have established a platform to study yeast circRNAs by RNA-seq. CircRNAs detection algorithms such as CIRI, find_circ, and NCLscan combined with customized templates were used to identify circRNAs in yeast. CircEFM5 was reported to be the most abundant circRNAs and was selected for further investigation under a variety of stress conditions such as stationary phase, temperature shift, high concentration of salt or metal, nitrogen starvation, and oxidative stress. By using RT-qPCR, I observed that the circular/linear ratio of EFM5 changed upon certain stresses, implicating that circEFM5 might be regulated upon stresses. My long-term goal is to comprehensively document yeast circRNAs and take the advantage of yeast genetics to investigate their functions in response to stresses in details. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T16:15:52Z (GMT). No. of bitstreams: 1 U0001-0608202017230700.pdf: 1840071 bytes, checksum: 280357ca6f1f85c9d0ca2cec897ac79a (MD5) Previous issue date: 2020 | en |
dc.description.tableofcontents | Verification Letter from the Oral Examination Committee i Abstract ii Abstract (In Chinese) iii Table of contents iv List of Figures vi List of Tables vii Introduction 1 1. CircRNAs, a distinct class of noncoding RNA 1 2. Biogenesis and degradation of circRNAs 2 3. Functions of circRNAs 4 4. CircRNAs are involved in cellular stress response 5 5. Yeast circRNA 7 Material and Methods 9 1. Yeast strains and culture conditions 9 2. Yeast total RNA extraction 9 3. Depletion of rRNA 10 4. RNase R 11 5. Detection of circRNA by RT-PCR 12 6. RNA-seq 13 7. RT-qPCR 13 8. Bioinformatics analysis 14 Results 15 1. Comprehensive investigation of yeast circRNAs 15 2. CircRNAs under stress …18 Discussion 34 References 37 | |
dc.language.iso | en | |
dc.title | 探討酵母菌環形核糖核酸與其在壓力環境下的表現 | zh_TW |
dc.title | Investigation of Yeast circular RNAs Under Stress | en |
dc.type | Thesis | |
dc.date.schoolyear | 108-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 莊樹諄(Trees-Juen Chuang),朱雪萍(Hsueh-Ping Chu) | |
dc.subject.keyword | 環形核糖核酸,核糖核酸測序,酵母菌,逆境,EFM5, | zh_TW |
dc.subject.keyword | circular RNA,RNA-seq,Yeast,Stress,EFM5, | en |
dc.relation.page | 46 | |
dc.identifier.doi | 10.6342/NTU202002565 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2020-08-07 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 基因體與系統生物學學位學程 | zh_TW |
顯示於系所單位: | 基因體與系統生物學學位學程 |
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