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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 TDP-43 Overexpression Enhances Exon-7 Inclusion during SMN Pre-mRNA Splicing |
Authors: | Bose Jayarama Krishnan 賈亞 |
Advisor: | 沈哲鯤 |
Keyword: | SMN基因, SMN Exon-7, |
Publication Year : | 2008 |
Degree: | 博士 |
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. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/41972 |
Fulltext Rights: | 有償授權 |
Appears in Collections: | 分子醫學研究所 |
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ntu-97-1.pdf Restricted Access | 2.6 MB | Adobe PDF |
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