Transposable Elements in TDP-43-Mediated Neurodegenerative Disorders

Li, W. H., Jin, Y., Prazak, L., Hammell, M., Dubnau, J. (2012) Transposable Elements in TDP-43-Mediated Neurodegenerative Disorders. PLoS ONE, 7 (9). ISSN 1932-6203

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URL: http://www.ncbi.nlm.nih.gov/pubmed/22957047
DOI: 10.1371/journal.pone.0044099

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.

Item Type: Paper
Uncontrolled Keywords: l1 retrotransposition rna targets tdp-43 expression brain cells dna mechanisms database neurons
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
diseases & disorders > nervous system diseases and disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transposons
CSHL Authors:
Communities: CSHL labs > Dubnau lab
CSHL labs > Hammell M. lab
CSHL Post Doctoral Fellows
Depositing User: Matt Covey
Date Deposited: 30 Jan 2013 17:40
Last Modified: 03 May 2013 13:43
PMCID: PMC3434193
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26993

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