Transposable elements in TDP-43-mediated neurodegenerative disorders.

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Transposable elements (TEs) show elevated expression in neurodegenerative disorders.
• TEs can be active during normal neurogenesis.

Purpose of the Study:

• To investigate the interaction between transposable elements (TEs) and the RNA-binding protein TDP-43.
• To explore the role of TE mis-regulation in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD).

Main Methods:

• Mining deep sequencing datasets of protein-RNA interactions and gene expression profiles.
• Analyzing TDP-43 binding to TE transcripts.
• Comparing TE-TDP-43 association in FTLD patients and mouse models.

Main Results:

• Extensive binding of TE transcripts to TDP-43 was uncovered.
• Association between TDP-43 and its TE targets is reduced in FTLD patients.
• A significant fraction of TEs bound by TDP-43 become de-repressed in mouse TDP-43 disease models.

Conclusions:

• TE mis-regulation is a potential contributor to TDP-43 related neurodegenerative diseases like ALS and FTLD.
• Disruption of TDP-43 binding to TEs may play a role in disease pathogenesis.