Graduate Program in Molecular and Cellular Biology, Stony Brook University, Stony Brook, New York, United States of America.
PLoS One. 2012;7(9):e44099. doi: 10.1371/journal.pone.0044099. Epub 2012 Sep 5.
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.
在几种神经退行性疾病中观察到特定转座因子 (TEs) 的表达水平升高。TEs 在正常神经发生过程中也可能活跃。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) 的关键 RNA 结合蛋白。其次，我们发现 TDP-43 与其许多 TE 靶标的关联在 FTLD 患者中减少。第三，我们发现 TDP-43 结合的很大一部分 TE 在小鼠 TDP-43 疾病模型中被去抑制。我们提出假说，即 TE 的错误调控导致 TDP-43 相关神经退行性疾病。
