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

Carlevaro-Fita, Joana; Polidori, Taisia; Das, Monalisa; Navarro, Carmen; Zoller, Tatjana I.; Johnson, Rory (2019). Ancient exapted transposable elements promote nuclear enrichment of human long noncoding RNAs. Genome research, 29(2), pp. 208-222. Cold Spring Harbor, N.Y 10.1101/gr.229922.117

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Carlevaro Fita, Joana; Polidori, Taisia and Johnson, Rory Baldwin

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1549-5469

Publisher:

Cold Spring Harbor, N.Y

Language:

English

Submitter:

Rebeka Gerber

Date Deposited:

04 Nov 2019 12:56

Last Modified:

04 Nov 2019 12:56

Publisher DOI:

10.1101/gr.229922.117

PubMed ID:

30587508

Additional Information:

Joana Carlevaro-Fita & Taisia Polidori contributed equally to this work.

BORIS DOI:

10.7892/boris.134309

URI:

https://boris.unibe.ch/id/eprint/134309

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