U6 snRNA expression prevents toxicity in TDP-43-knockdown cells
Publication Date
November 10, 2017
Authors
Masao Yahara, Akira Kitamura & Masataka Kinjo
Volume
12
Issue
11
Pages
e0187813
DOI
https://dx.plos.org/10.1371/journal.pone.0187813
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0187813
Scopus
85033570746
Mendeley
http://www.mendeley.com/research/u6-snrna-expression-prevents-toxicity-tdp43knockdown-cells
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Mendeley | Further Information

{"title"=>"U6 snRNA expression prevents toxicity in TDP-43-knockdown cells", "type"=>"journal", "authors"=>[{"first_name"=>"Masao", "last_name"=>"Yahara", "scopus_author_id"=>"57062840300"}, {"first_name"=>"Akira", "last_name"=>"Kitamura", "scopus_author_id"=>"57200132238"}, {"first_name"=>"Masataka", "last_name"=>"Kinjo", "scopus_author_id"=>"7006537664"}], "year"=>2017, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"85033570746", "pmid"=>"29125873", "pui"=>"619191417", "issn"=>"19326203", "isbn"=>"1111111111", "scopus"=>"2-s2.0-85033570746", "doi"=>"10.1371/journal.pone.0187813"}, "id"=>"7c87f522-30f1-3e31-b2b7-c467c5e6e7c4", "abstract"=>"Depletion of amyotrophic lateral sclerosis (ALS)-associated transactivation response (TAR) RNA/DNA-binding protein 43 kDa (TDP-43) alters splicing efficiency of multiple transcripts and results in neuronal cell death. TDP-43 depletion can also disturb expression levels of small nuclear RNAs (snRNAs) as spliceosomal components. Despite this knowledge, the relationship between cell death and alteration of snRNA expression during TDP-43 deple- tion remains unclear. Here, we knocked down TDP-43 in murine neuroblastoma Neuro2A cells and found a time lag between efficient TDP-43 depletion and appearance of cell death, suggesting that several mechanisms mediate between these two events. The amount of U6 snRNA was significantly decreased during TDP-43 depletion prior to increase of cell death, whereas that of U1, U2, and U4 snRNAs was not. Downregulation of U6 snRNA led to cell death, whereas transient exogenous expression of U6 snRNA counteracted the effect of TDP-43 knockdown on cell death, and slightly decreased the mis-splicing rate of Dnajc5 and Sortilin 1 transcripts, which are assisted by TDP-43. These results suggest that regula- tion of the U6 snRNA expression level by TDP-43 is a key factor in the increase in cell death upon TDP-43 loss-of-function. Introduction", "link"=>"http://www.mendeley.com/research/u6-snrna-expression-prevents-toxicity-tdp43knockdown-cells", "reader_count"=>10, "reader_count_by_academic_status"=>{"Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Master"=>2, "Researcher"=>3}, "reader_count_by_user_role"=>{"Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Master"=>2, "Researcher"=>3}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>4, "Neuroscience"=>1}, "reader_count_by_subdiscipline"=>{"Neuroscience"=>{"Neuroscience"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}}, "group_count"=>0}

Scopus | Further Information

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