https://scholars.lib.ntu.edu.tw/handle/123456789/160120
標題: | 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 |
作者: | 賈亞 Krishnan, Bose Jayarama |
關鍵字: | SMN基因;SMN Exon-7 | 公開日期: | 2008 | 摘要: | 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 multifunctionalNA-binding protein for a diverse set of cellular activities. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/178689 |
顯示於: | 分子醫學研究所 |
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ntu-97-D91448007-1.pdf | 23.32 kB | Adobe PDF | 檢視/開啟 |
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