Ancient exapted transposable elements promote nuclear enrichment of human long noncoding RNAs
- Joana Carlevaro-Fita1,2,3,5,
- Taisia Polidori1,2,3,5,
- Monalisa Das1,2,5,
- Carmen Navarro4,
- Tatjana I. Zoller1,2 and
- Rory Johnson1,2
- 1Department for BioMedical Research (DBMR), University of Bern, 3008 Bern, Switzerland;
- 2Department of Medical Oncology, Inselspital, University Hospital and University of Bern, 3010 Bern, Switzerland;
- 3Graduate School of Cellular and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland;
- 4Department of Computer Science and Artificial Intelligence, University of Granada, 18071 Granada, Spain
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↵5 These authors contributed equally to this work.
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.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.229922.117.
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Freely available online through the Genome Research Open Access option.
- Received January 23, 2018.
- Accepted December 18, 2018.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
