Transposable elements in TDP-43-mediated neurodegenerative disorders.
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...
| Hauptverfasser: | , , , , |
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| Format: | Artikel |
| Sprache: | English |
| Veröffentlicht: |
Public Library of Science (PLoS)
2012-01-01
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| Schriftenreihe: | PLoS ONE |
| Online Zugang: | http://europepmc.org/articles/PMC3434193?pdf=render |
| Zusammenfassung: | 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. |
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| ISSN: | 1932-6203 |