Format

Send to

Choose Destination
Nat Commun. 2019 Nov 13;10(1):5137. doi: 10.1038/s41467-019-12970-4.

The Firre locus produces a trans-acting RNA molecule that functions in hematopoiesis.

Author information

1
Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
2
Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK.
3
BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, USA.
4
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.
5
Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, 77 Louis Pasteur Avenue, Boston, MA, USA.
6
Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
7
The Jackson Laboratory, JAX Genomic Medicine, Farmington, CT, USA.
8
Department of Pathology and Laboratory Medicine, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA, USA.
9
Department of Immunobiology and Howard Hughes Medical Institute, Yale University, School of Medicine, New Haven, CT, USA.
10
Department of Genetics, Harvard Medical School, Boston, MA, USA.
11
Howard Hughes Medical Institute, Boston, MA, USA.
12
Joslin Diabetes Center, Boston, MA, USA.
13
Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA. john.rinn@colorado.edu.
14
BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, USA. john.rinn@colorado.edu.

Abstract

RNA has been classically known to play central roles in biology, including maintaining telomeres, protein synthesis, and in sex chromosome compensation. While thousands of long noncoding RNAs (lncRNAs) have been identified, attributing RNA-based roles to lncRNA loci requires assessing whether phenotype(s) could be due to DNA regulatory elements, transcription, or the lncRNA. Here, we use the conserved X chromosome lncRNA locus Firre, as a model to discriminate between DNA- and RNA-mediated effects in vivo. We demonstrate that (i) Firre mutant mice have cell-specific hematopoietic phenotypes, and (ii) upon exposure to lipopolysaccharide, mice overexpressing Firre exhibit increased levels of pro-inflammatory cytokines and impaired survival. (iii) Deletion of Firre does not result in changes in local gene expression, but rather in changes on autosomes that can be rescued by expression of transgenic Firre RNA. Together, our results provide genetic evidence that the Firre locus produces a trans-acting lncRNA that has physiological roles in hematopoiesis.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center