Differential Display Detects Host Nucleic Acid Motifs Altered in Scrapie-Infected Brain

Transposable Elements in TDP-43-Mediated Neurodegenerative Disorders

“…On the other hand, there also is emerging evidence that unregulated activation of TEs is associated with neuropathology. TE activation in brain has been observed in macular degeneration [14], Rett syndrome [11], Prion diseases [13], [29], Fragile-X associated tremor/ataxia syndrome (FXTAS) [15] and ALS [12]. Moreover, for the cases of macular degeneration and FXTAS, there is evidence that activation of SINEs and an LTR-retrotransposon respectively may contribute to the observed pathology [14], [15].…”

“…Although most investigations have naturally focused on the germline, where new insertions are heritable and thus favored by transposon evolution, somatic tissues also have an active transposon silencing mechanism whose functional significance is less understood. An emerging literature has established that certain TEs are normally active in brain [6], [7], [8], [9] and elevated expression of some LINE, SINE (which are non-LTR retrotransposons) and LTR elements have been correlated with several neurodegenerative disorders [10], [11], [12], [13], [14], [15], [16]. We therefore investigated whether the RNA targets of TDP-43 include transposon-derived transcripts.…”

The Complete Genome Sequences, Unique Mutational Spectra, and Developmental Potency of Adult Neurons Revealed by Cloning

“…In addition, somatic mobile element insertions (MEIs) have been identified in mouse (Muotri et al, 2005; Muotri et al, 2009), human (Baillie et al, 2011; Coufal et al, 2009; Evrony et al, 2012; Upton et al, 2015), and fly neurons (Li et al, 2013; Perrat et al, 2013), although these studies report widely varying estimates, ranging from 0.07 to 129 per neuron (Coufal et al, 2009; Evrony et al, 2012; Evrony et al, 2014; Perrat et al, 2013; Upton et al, 2015). Understanding whether this variation is due to neuronal subtype diversity or reflects methodological differences is key to discerning the functional impact of MEIs, which have been postulated to contribute to neural diversity (Muotri et al, 2005; Singer et al, 2010; Upton et al, 2015) and/or neurological disorders (Bundo et al, 2014; Coufal et al, 2011; Douville et al, 2011; Jeong et al, 2010; Kaneko et al, 2011; Lathe and Harris, 2009; Li et al, 2012; Muotri et al, 2010; Tan et al, 2012). Together these intriguing first overviews of neuronal genome diversity highlight the importance of applying increasingly sensitive methods to decipher the genome sequences of neurons and survey the complete landscape of neuronal somatic mutations.…”

Activation of transposable elements during aging and neuronal decline in Drosophila

“…However, because TEs are capable of replicating and inserting into new positions in the genome, they represent a massive reservoir of potential genomic instability as well as RNA-level toxicity. In fact, TE activation has been correlated with several neurodegenerative disorders 6–13 .…”

“…This phenomenology has lead to the suggestion that regulated TE jumping provides a source of somatic mosaicism that may contribute to normal brain physiology, although such functional effects remain to be established. On the other hand, LINE, SINE and LTR elements are de-repressed in a variety of neurodegenerative diseases 6–13 , suggesting the possibility that misregulation of TEs is detrimental. The results reported here, together with the above literature, suggest the novel hypothesis that TE activation with age or disease may contribute to neuronal decline.…”