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http://purl.uniprot.org/citations/22900096http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22900096http://www.w3.org/2000/01/rdf-schema#comment"Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease caused by selective loss of motor neurons. In the ALS motor neurons, TAR DNA-binding protein of 43 kDa (TDP-43) is dislocated from the nucleus to cytoplasm and forms inclusions, suggesting that loss of a nuclear function of TDP-43 may underlie the pathogenesis of ALS. TDP-43 functions in RNA metabolism include regulation of transcription, mRNA stability, and alternative splicing of pre-mRNA. However, a function of TDP-43 in tissue affected with ALS has not been elucidated. We sought to identify the molecular indicators reflecting on a TDP-43 function. Using exon array analysis, we observed a remarkable alteration of splicing in the polymerase delta interacting protein 3 (POLDIP3) as a result of the depletion of TDP-43 expression in two types of cultured cells. In the cells treated with TDP-43 siRNA, wild-type POLDIP3 (variant-1) decreased and POLDIP3 lacking exon 3 (variant-2) increased. The RNA binding ability of TDP-43 was necessary for inclusion of POLDIP3 exon 3. Moreover, we found an increment of POLDIP3 variant-2 mRNA in motor cortex, spinal cord and spinal motor neurons collected by laser capture microdissection with ALS. Our results suggest a loss of TDP-43 function in tissues affected with ALS, supporting the hypothesis that a loss of function of TDP-43 underlies the pathogenesis of ALS."xsd:string
http://purl.uniprot.org/citations/22900096http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0043120"xsd:string
http://purl.uniprot.org/citations/22900096http://purl.uniprot.org/core/author"Kato T."xsd:string
http://purl.uniprot.org/citations/22900096http://purl.uniprot.org/core/author"Nishizawa M."xsd:string
http://purl.uniprot.org/citations/22900096http://purl.uniprot.org/core/author"Miyashita A."xsd:string
http://purl.uniprot.org/citations/22900096http://purl.uniprot.org/core/author"Kuwano R."xsd:string
http://purl.uniprot.org/citations/22900096http://purl.uniprot.org/core/author"Takahashi H."xsd:string
http://purl.uniprot.org/citations/22900096http://purl.uniprot.org/core/author"Takahashi M."xsd:string
http://purl.uniprot.org/citations/22900096http://purl.uniprot.org/core/author"Watanabe N."xsd:string
http://purl.uniprot.org/citations/22900096http://purl.uniprot.org/core/author"Kondo C."xsd:string
http://purl.uniprot.org/citations/22900096http://purl.uniprot.org/core/author"Onodera O."xsd:string
http://purl.uniprot.org/citations/22900096http://purl.uniprot.org/core/author"Ishihara T."xsd:string
http://purl.uniprot.org/citations/22900096http://purl.uniprot.org/core/author"Kakita A."xsd:string
http://purl.uniprot.org/citations/22900096http://purl.uniprot.org/core/author"Shiga A."xsd:string
http://purl.uniprot.org/citations/22900096http://purl.uniprot.org/core/author"Yokoseki A."xsd:string
http://purl.uniprot.org/citations/22900096http://purl.uniprot.org/core/author"Kuwabara M."xsd:string
http://purl.uniprot.org/citations/22900096http://purl.uniprot.org/core/author"Yamahira A."xsd:string
http://purl.uniprot.org/citations/22900096http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22900096http://purl.uniprot.org/core/name"PLoS One"xsd:string
http://purl.uniprot.org/citations/22900096http://purl.uniprot.org/core/pages"e43120"xsd:string
http://purl.uniprot.org/citations/22900096http://purl.uniprot.org/core/title"Alteration of POLDIP3 splicing associated with loss of function of TDP-43 in tissues affected with ALS."xsd:string
http://purl.uniprot.org/citations/22900096http://purl.uniprot.org/core/volume"7"xsd:string
http://purl.uniprot.org/citations/22900096http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/22900096
http://purl.uniprot.org/citations/22900096http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/22900096