Ancient exapted transposable elements drive nuclear localisation of lncRNAs

The sequence domains underlying long noncoding RNA (lncRNA) activities, including their characteristic nuclear localisation, remain largely unknown. One hypothetical source of such domains are neofunctionalised fragments of transposable elements (TEs), otherwise known as RIDLs (Repeat Insertion Domains of Long Noncoding RNA). We here present a transcriptome-wide map of putative RIDLs in human, using evidence from insertion frequency, strand bias and evolutionary conservation of sequence and structure. In the exons of GENCODE v21 lncRNAs, we identify a total of 5374 RIDLs in 3566 gene loci. RIDL-containing lncRNAs are over-represented in functionally-validated and disease-associated genes. By integrating this RIDL map with global lncRNA subcellular localisation data, we uncover a cell-type-invariant and dose-dependent relationship between LINE2 and MIR elements and nuclear-cytoplasmic distribution. Experimental validations establish causality, showing that these RIDLs drive the nuclear localisation of their host lncRNA. Together these data represent the first map of TE-derived functional domains, and suggest a global role for TEs as nuclear localisation signals of lncRNAs.