About: Transcriptomic Changes Due to Cytoplasmic TDP-43 Expression Reveal Dysregulation of Histone Transcripts and Nuclear Chromatin

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About: Transcriptomic Changes Due to Cytoplasmic TDP-43 Expression Reveal Dysregulation of Histone Transcripts and Nuclear Chromatin Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Transcriptomic Changes Due to Cytoplasmic TDP-43 Expression Reveal Dysregulation of Histone Transcripts and Nuclear Chromatin
Creator	Xu, Yan Amlie-Wolf, Alexandre Dragomir, Isabelle Ryvkin, Paul Tong, Rui Wang, Li-San Gregory, Brian Kwong, Linda Lee, Edward Trojanowski, John Van Deerlin, Vivianna Lee, M.-Y Suh, Eunran
Source	PMC
abstract	TAR DNA-binding protein 43 (TDP-43) is normally a nuclear RNA-binding protein that exhibits a range of functions including regulation of alternative splicing, RNA trafficking, and RNA stability. However, in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP), TDP-43 is abnormally phosphorylated, ubiquitinated, and cleaved, and is mislocalized to the cytoplasm where it forms distinctive aggregates. We previously developed a mouse model expressing human TDP-43 with a mutation in its nuclear localization signal (ΔNLS-hTDP-43) so that the protein preferentially localizes to the cytoplasm. These mice did not exhibit a significant number of cytoplasmic aggregates, but did display dramatic changes in gene expression as measured by microarray, suggesting that cytoplasmic TDP-43 may be associated with a toxic gain-of-function. Here, we analyze new RNA-sequencing data from the ΔNLS-hTDP-43 mouse model, together with published RNA-sequencing data obtained previously from TDP-43 antisense oligonucleotide (ASO) knockdown mice to investigate further the dysregulation of gene expression in the ΔNLS model. This analysis reveals that the transcriptomic effects of the overexpression of the ΔNLS-hTDP-43 transgene are likely due to a gain of cytoplasmic function. Moreover, cytoplasmic TDP-43 expression alters transcripts that regulate chromatin assembly, the nucleolus, lysosomal function, and histone 3’ untranslated region (UTR) processing. These transcriptomic alterations correlate with observed histologic abnormalities in heterochromatin structure and nuclear size in transgenic mouse and human brains.
has issue date	2015-10-28(xsd:dateTime)
bibo:doi	10.1371/journal.pone.0141836
bibo:pmid	26510133
has license	cc-by
sha1sum (hex)	8bb5f822c7bae1c50b1d5b7a9da329a1f9d8aee2
schema:url	https://doi.org/10.1371/journal.pone.0141836
resource representing a document's title	Transcriptomic Changes Due to Cytoplasmic TDP-43 Expression Reveal Dysregulation of Histone Transcripts and Nuclear Chromatin
has PubMed Central identifier	PMC4624943
has PubMed identifier	26510133
schema:publication	PLoS One
resource representing a document's body	covid:8bb5f822c7bae1c50b1d5b7a9da329a1f9d8aee2#body_text
is schema:about of	named entity 'cytoplasmic' named entity 'mice' named entity 'TDP-43' named entity 'trafficking' named entity 'heterochromatin' named entity 'microarray' named entity 'Cytoplasmic' named entity 'AGGREGATES' named entity 'TRAFFICKING' named entity 'SIGNIFICANT' covid:arg/8bb5f822c7bae1c50b1d5b7a9da329a1f9d8aee2 named entity 'NUCLEOLUS' named entity 'MEASURED' named entity 'TRANSCRIPTS' named entity 'DUE TO' named entity 'CHANGES' named entity 'LIKELY' named entity 'STRUCTURE' named entity 'A MOUSE' named entity 'KNOCKDOWN MICE' named entity 'EXHIBIT' named entity 'FORMS' named entity 'ITS' named entity 'MICROARRAY' named entity 'OBSERVED' named entity 'ASSOCIATED WITH' named entity 'OBTAINED' named entity 'TOXIC' named entity 'TDP-43' named entity 'NUCLEAR CHROMATIN' named entity 'EXPRESSION' named entity 'OVEREXPRESSION' named entity 'CYTOPLASMIC' named entity 'CLEAVED' named entity 'TRANSGENIC MOUSE' named entity 'SEQUENCING DATA' named entity 'AMYOTROPHIC LATERAL SCLEROSIS' named entity 'WHERE' named entity 'CHANGES' named entity 'EXPRESSION' named entity 'HISTONE' named entity 'CYTOPLASMIC' named entity 'TAR DNA-BINDING PROTEIN 43' named entity 'HETEROCHROMATIN' named entity 'OF-' named entity 'NUCLEAR SIZE' named entity 'RNA' named entity 'HUMAN' named entity 'PHOSPHORYLATED' named entity 'BUT' named entity 'ALTERNATIVE SPLICING' named entity 'INCLUSIONS' named entity 'TRANSCRIPTS' named entity 'NEW' named entity 'FUNCTION' named entity 'FRONTOTEMPORAL LOBAR DEGENERATION' named entity 'PUBLISHED' named entity 'MUTATION' named entity 'CYTOPLASM' named entity 'EXHIBITS' named entity 'REGULATE' named entity 'PROCESSING' named entity 'NUMBER OF' named entity 'FUNCTIONS' named entity 'UBIQUITINATED' named entity 'TO INVESTIGATE' named entity 'PROTEIN ' named entity 'MAY BE' named entity 'MISLOCALIZED'

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