論文 - 詳細
| RRC ID | 54185 |
|---|---|
| 著者 | Yahara M, Kitamura A, Kinjo M. |
| タイトル | U6 snRNA expression prevents toxicity in TDP-43-knockdown cells. |
| ジャーナル | PLoS One |
| 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 depletion 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 regulation 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. |
| 巻・号 | 12(11) |
| ページ | e0187813 |
| 公開日 | 2017-11-10 |
| DOI | 10.1371/journal.pone.0187813 |
| PII | PONE-D-17-20742 |
| PMID | 29125873 |
| PMC | PMC5681290 |
| MeSH | Animals Apoptosis Cell Line, Tumor DNA-Binding Proteins / genetics* Down-Regulation Gene Knockout Techniques Mice RNA, Small Nuclear / genetics* |
| IF | 2.74 |
| 引用数 | 4 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 8 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pSuperior.neo-U6snRNA (RDB16712) |