The Role of Transposable Elements in Health and Diseases of the Central Nervous System

Abstract

First discovered in maize by Barbara McClintock in the 1940s, transposable elements (TEs) are DNA sequences that in some cases have the ability to move along chromosomes or "transpose" in the genome. This revolutionary finding was initially met with resistance by the scientific community and viewed by some as heretical. A large body of knowledge has accumulated over the last 60 years on the biology of TEs. Indeed, it is now known that TEs can generate genomic instability and reconfigure gene expression networks both in the germline and somatic cells. This review highlights recent findings on the role of TEs in health and diseases of the CNS, which were presented at the 2013 Society for Neuroscience meeting. The work of the speakers in this symposium shows that TEs are expressed and active in the brain, challenging the dogma that neuronal genomes are static and revealing that they are susceptible to somatic genomic alterations. These new findings on TE expression and function in the CNS have major implications for understanding the neuroplasticity of the brain, which could hypothetically have a role in shaping individual behavior and contribute to vulnerability to disease.

The Persistent Contributions of RNA to Eukaryotic Gen(om)e Architecture and Cellular Function

“…Somatic LINE element integrations even have been implied in the development of the brain (Muotri et al 2005;Coufal et al 2009;Faulkner et al 2009;Singer et al 2010;Baillie et al 2011;Upton et al 2011;Perrat et al 2013;Reilly et al 2013). Either TEs are chock full of regulatory motifs and control elements, which can be argued in case of promoters, for example, LTRs (Feuchter and Mager 1990), or it is the fact that TEs are defined and designated nucleic acid sequences (nuons) (Brosius and Gould 1992) and, therefore, receive more attention instead of randomized and anonymous sequences in attempts to investigate their functions.…”

Age‐associated de‐repression of retrotransposons in the Drosophila fat body, its potential cause and consequence

“…Since accumulation of DNA damage is known to cause cellular senescence and organismal aging (Best, 2009), activation of TEs could contribute to organismal aging. Although TE activation during development has also been implicated as important for proper development of the nervous system (Reilly et al ., 2013), in most settings TEs are repressed by the heterochromatin state to prevent uncontrolled transposition (Levin & Moran, 2011; Wood & Helfand, 2013). Therefore, in addition to de‐repression of genes, the age‐associated heterochromatin loss could also cause an increased expression of TEs, which would in turn contribute to age‐associated cell and organ defects.…”

Stress and the dynamic genome: Steroids, epigenetics, and the transposome

“…They have been successfully coopted by the mammalian immune system to provide antibody diversity, and a similar process may be at work in generating genomic, and by extension behavioral, diversity in the brain (17,97,111). Our work suggests that the brain may also need to regulate retrotransposon RNA expression on a rapid and dynamic basis and that this regulation could have adaptive significance (16).…”

“…In the nervous system, dysregulation of transposon expression has been linked to retinal degeneration (57), schizophrenia (58), alcoholism, posttraumatic stress disorder (PTSD) (59,60), and a number of neurodegenerative disorders (17,61). Recent work has identified excess transposon expression in the Drosophila melanogaster brain as a factor in age-related neurodegeneration.…”

“…The desire to understand how environmental stress transduces its effects into lasting changes on physiology and behavior, which can vary even among genetically identical individuals, has led scientists to hypothesize that epigenetic factors might provide an explanatory mechanism (1,13,14). The introduction of next-generation sequencing technologies to the exploration of epigenetics and stress neurobiology has led to greater attention to the possibility that the largely unexplored genomic space represented by retrotransposons might also have functional significance for brain function and stress susceptibility (15)(16)(17).…”