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Transposable Elements in TDP-43-Mediated Neurodegenerative Disorders

2012; Public Library of Science; Volume: 7; Issue: 9 Linguagem: Inglês

10.1371/journal.pone.0044099

1932-6203

Wanhe Li, Ying Jin, Lisa Prazak, Molly Hammell, Josh Dubnau,

Chromosomal and Genetic Variations

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.