title: Transposable elements in TDP-43-mediated neurodegenerative disorders.
abstract: 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.
authors.affiliation: Graduate Program in Molecular and Cellular Biology, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Wanhe
authors.initials: W
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
authors.forename: Lisa
authors.initials: L
authors.lastname: Prazak
authors.forename: Molly
authors.initials: M
authors.lastname: Hammell
authors.forename: Josh
authors.initials: J
authors.lastname: Dubnau
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins / Q000235:genetics*; D005625:Frontal Lobe / Q000473:pathology; D020869:Gene Expression Profiling; D016678:Genome; D006801:Humans; D051379:Mice; D015233:Models, Statistical; D008969:Molecular Sequence Data; D019636:Neurodegenerative Diseases / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D051381:Rats
chemical_list: D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D012313:RNA