Expressing genes do not forget their LINEs: transposable elements and gene expression

Abstract

1. ABSTRACT Historically the accumulated mass of mammalian transposable elements (TEs), particularly those located within gene boundaries, was viewed as a genetic burden potentially detrimental to the genomic landscape. This notion has been strengthened by the discovery that transposable sequences can alter the architecture of the transcriptome, not only through insertion, but also long after the integration process is completed. Insertions previously considered harmless are now known to impact the expression of host genes via modification of the transcript quality or quantity, transcriptional interference, or by the control of pathways that affect the mRNA life-cycle. Conversely, several examples of the evolutionary advantageous impact of TEs on the host gene structure that diversified the cellular transcriptome are reported. TE-induced changes in gene expression can be tissue-or disease-specific, raising the possibility that the impact of TE sequences may vary during development, among normal cell types, and between normal and disease-affected tissues. The understanding of the rules and abundance of TE-interference with gene expression is in its infancy, and its contribution to human disease and/or evolution remains largely unexplored.

Is junk DNA bunk? A critique of ENCODE

“…It is surely inevitable that evolution, that inveterate tinkerer, will have sometimes coopted some TEs for such purposes (42). However, it is an overenthusiastic extrapolation to describe TEs as a class as "active and lively members of the genomic regulatory community."…”

“…The publications by Lynch et al (24) and Lynch (39,49) have effectively argued that drift operating in very small populations will (by chance) encourage accumulation of DNA that can add to C-value and might, in the future, come in handy. Selection at the suborganismal (selfish DNA) level may also seem to be future-directed: TEs do sometimes later become useful through cooptation or general effects on the generation of novelty (42,50). Indeed, Fedoroff (51) has recently proposed that TEs should not be described pejoratively as "selfish" and that the prevailing view-that the epigenetic silencing mechanisms that eukaryotes use to limit TE replication arose to do just that-puts the evolutionary cart before the horse.…”

LINE-1 activity as molecular basis for genomic instability associated with light exposure at night

“…15,16 In addition to cumulative L1 activity in any given genome, the differences in the function of Keywords: aging, shift-work, cancer, DNA damage, genomic instability, light exposure at night, LINE-1, melatonin, melatonin receptor, retroelements available cellular pathways suppressing L1 activity may contribute to the reported variation in L1 retrotransposition among individual genomes. [17][18][19] The increasing list of host proteins and pathways reported to suppress L1 mobilization in cultured cells is an implicit indication of the importance of minimizing L1-associated damage (Fig.…”

Restless Genomes

“…Integration of these elements within human intronic regions most of the time does not prevent gene expression, but may reduce cell fitness or function under certain stress conditions or in combination with other genomic alterations [reviewed in Kines and Belancio, 2011]. Because L1 and SVA elements contain functional splice and polyadenylation sites (Belancio et al ., 2006, 2008b; Hancks et al ., 2009; Perepelitsa-Belancio and Deininger, 2003) and Alu elements are prone to acquiring functional splice sites through random mutations long after the integration process is completed.…”