Transposable elements in TDP-43-mediated neurodegenerative disorders.
Transposable elements in TDP-43-mediated neurodegenerative disorders.
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DOI：
10.1371/journal.pone.0044099
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Dubnau J
中科院分区：
文献类型：
--
作者：
Li W;Jin Y;Prazak L;Hammell M;Dubnau J
在一些神经退行性疾病中观察到了特定转座元件(TES)的表达升高。在正常的神经发生过程中，TES也可以是活跃的。通过挖掘一系列蛋白质-RNA相互作用和基因表达谱的深度测序数据集，我们发现TE转录本与TDP-43广泛结合，TDP-43是肌萎缩侧索硬化症(ALS)和额颞叶变性(FTLD)的核心RNA结合蛋白。其次，我们发现FTLD患者TDP-43与其许多TE靶点之间的关联性降低。第三，我们发现，在小鼠TDP-43疾病模型中，TDP-43结合的TES的很大一部分被解除抑制。我们提出的假说是，TE调节失调与TDP-43相关的神经退行性疾病有关。
Elevated expression of specific transposable elements (TEs) has been observed in several neurodegenerative disorders. TEs also can be active during normal neurogenesis. By mining a series of deep sequencing datasets of protein-RNA interactions and of gene expression profiles, we uncovered extensive binding of TE transcripts to TDP-43, an RNA-binding protein central to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Second, we find that association between TDP-43 and many of its TE targets is reduced in FTLD patients. Third, we discovered that a large fraction of the TEs to which TDP-43 binds become de-repressed in mouse TDP-43 disease models. We propose the hypothesis that TE mis-regulation contributes to TDP-43 related neurodegenerative diseases.