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Nat Commun. 2016 Mar 24;7:11021. doi: 10.1038/ncomms11021.

Function and evolution of local repeats in the Firre locus.

Hacisuleyman E1,2,3, Shukla CJ2,3,4, Weiner CL1,2,3, Rinn JL2,3,5.

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Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Department of Stem Cell and Regenerative Biology, Harvard University7 Divinity Avenue, Room 305, Cambridge, Massachusetts 02138, USA.
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA.
Department of Biological and Biomedical Sciences, Harvard University, Boston, Massachusetts 02115, USA.
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.


More than half the human and mouse genomes are comprised of repetitive sequences, such as transposable elements (TEs), which have been implicated in many biological processes. In contrast, much less is known about other repeats, such as local repeats that occur in multiple instances within a given locus in the genome but not elsewhere. Here, we systematically characterize local repeats in the genomic locus of the Firre long noncoding RNA (lncRNA). We find a conserved function for the RRD repeat as a ribonucleic nuclear retention signal that is sufficient to retain an otherwise cytoplasmic mRNA in the nucleus. We also identified a repeat, termed R0, that can function as a DNA enhancer element within the intronic sequences of Firre. Collectively, our data suggest that local repeats can have diverse functionalities and molecular modalities in the Firre locus and perhaps more globally in other lncRNAs.

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