RT Journal
A1 Carlevaro-Fita, Joana
A1 Polidori, Taisia
A1 Das, Monalisa
A1 Navarro, Carmen
A1 Zoller, Tatjana I.
A1 Johnson, Rory
T1 Ancient exapted transposable elements promote nuclear enrichment of human long noncoding RNAs
JF Genome Research 
JO Genome Research 
YR 2019 
FD February 01 
VO 29 
IS 2 
SP 208 
OP 222 
DO 10.1101/gr.229922.117 
UL http://genome.cshlp.org/content/29/2/208.abstract 
AB 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 dose-dependent 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.