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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 沈哲鯤 | |
dc.contributor.author | Bose Jayarama Krishnan | en |
dc.contributor.author | 賈亞 | zh_TW |
dc.date.accessioned | 2021-06-15T00:39:56Z | - |
dc.date.available | 2008-12-18 | |
dc.date.copyright | 2008-12-18 | |
dc.date.issued | 2008 | |
dc.date.submitted | 2008-10-07 | |
dc.identifier.citation | References
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/41972 | - |
dc.description.abstract | TDP-43 is a highly conserved, 43 kDa RNA-binding protein implicated to play a role in transcription repression, nuclear organization, and alternative splicing. More recently, TDP-43 has been identified as the major disease protein of several neurodegenerative diseases including frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS). For the splicing activity, TDP-43 has been shown to be mainly an exon-skipping promoter. In this study using the Survival of Motor Neuron (SMN) minigenes as the reporters in transfection assay, I show for the first time that TDP-43 could also act as an exon-inclusion factor. Furthermore, both RRM domains are required for the ability of TDP-43 to enhance the SMN2 exon 7-inclusion. Combined protein-immunoprecipitation (IP) and RNA-IP experiments also suggested that the exon-inclusion by TDP-43 might be mediated by multimeric complex(es) consisting of TDP-43 interacting with other splicing factors including Htra2-β1. My data further evidences TDP-43 as a multifunctional
RNA-binding protein for a diverse set of cellular activities. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T00:39:56Z (GMT). No. of bitstreams: 1 ntu-97-D91448007-1.pdf: 2658715 bytes, checksum: af433b0836bce64a3ca29e587c24ce0f (MD5) Previous issue date: 2008 | en |
dc.description.tableofcontents | Table of Contents 1
Abstract 3 Introduction 4 Experimental rationale 18 Materials and Methods 19 Plasmid Constructs 19 Expression Vectors 20 DNA transfection and In vivo splicing assay 20 RNA immunoprecipitation (RNA-IP) 21 Protein-protein interaction assay 22 Oligonucleotide preparation by in vitro transcription 23 In vitro RNA-protein binding 24 Immunostaining 25 RNA interference (RNAi) assay 25 Primers Used 26 Results 29 TDP-43 interacted with the SMN transcripts 29 TDP-43 stimulated the inclusion of exon 7 during splicing of SMN2 pre-mRNA 30 TDP-43 overexpression does not affect SMN1 splicing 31 Differential requirement of RRM domains for RNA binding and Splicing 31 The AG-rich SE2 element of the SMN transcripts was required for TDP-43 stimulated exon 7-inclusion 33 TDP-43 binding with SMN-mRNA was not sequence specific 35 TDP-43 interacts with Htra2-β1 ......................... 36 Co-expression of TDP-43 and Htra2-β1................... 37 RNAi knockdown of TDP-43 had no effect on SMN splicing .. 38 Transgenic mice ....................................... 39 References .................................46 Figure....................................53 Appendix ......................................70 | |
dc.language.iso | en | |
dc.title | TDP-43大量表現對於包含SMN基因之Pre-mRNA的Exon-7剪接之增益 | zh_TW |
dc.title | TDP-43 Overexpression Enhances Exon-7 Inclusion during SMN Pre-mRNA Splicing | en |
dc.type | Thesis | |
dc.date.schoolyear | 97-1 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 呂勝春,譚琬玉,李鴻,鄭淑珍 | |
dc.subject.keyword | SMN基因, | zh_TW |
dc.subject.keyword | SMN Exon-7, | en |
dc.relation.page | 73 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2008-10-07 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
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