Ancient exapted transposable elements promote nuclear enrichment of human long noncoding RNAs
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Cold Spring Harbor Laboratory Press
Fecha
2019Referencia bibliográfica
Carlevaro-Fita, J., Polidori, T., Das, M., Navarro, C., & Johnson, R. (2017). Ancient exapted transposable elements drive nuclear localisation of lncRNAs. bioRxiv, 189753.
Patrocinador
This research was funded by the NCCR “RNA & Disease” funded by the Swiss National Science Foundation and by the Medical Faculty of the University and University Hospital of Bern.Resumen
The sequence domains underlying long noncoding RNA (lncRNA) activities, including their characteristic nuclear enrichment,
remain largely unknown. It has been proposed that these domains can originate from neofunctionalized fragments of
transposable elements (TEs), otherwise known as RIDLs (repeat insertion domains of lncRNA), although just a handful have
been identified. It is challenging to distinguish functional RIDL instances against a numerous genomic background of neutrally
evolving TEs. We here show evidence that a subset of TE types experience evolutionary selection in the context of
lncRNA exons. Together these comprise an enrichment group of 5374 TE fragments in 3566 loci. Their host lncRNAs
tend to be functionally validated and associated with disease. This RIDL group was used to explore the relationship between
TEs and lncRNA subcellular localization. By using global localization data from 10 human cell lines, we uncover a dosedependent
relationship between nuclear/cytoplasmic distribution and evolutionarily conserved L2b, MIRb, and MIRc elements.
This is observed in multiple cell types and is unaffected by confounders of transcript length or expression.
Experimental validation with engineered transgenes shows that these TEs drive nuclear enrichment in a natural sequence
context. Together these data reveal a role for TEs in regulating the subcellular localization of lncRNAs.