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Genome Res. 2019 Feb;29(2):208-222. doi: 10.1101/gr.229922.117. Epub 2018 Dec 26.

Ancient exapted transposable elements promote nuclear enrichment of human long noncoding RNAs.

Author information

1
Department for BioMedical Research (DBMR), University of Bern, 3008 Bern, Switzerland.
2
Department of Medical Oncology, Inselspital, University Hospital and University of Bern, 3010 Bern, Switzerland.
3
Graduate School of Cellular and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland.
4
Department of Computer Science and Artificial Intelligence, University of Granada, 18071 Granada, Spain.
#
Contributed equally

Abstract

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.

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