Document Type
Article
Publication Date
11-13-2019
Keywords
JGM
JAX Source
Nat Commun 2019 Nov 13; 10(1):5137
Volume
10
Issue
1
First Page
5137
Last Page
5137
ISSN
2041-1723
PMID
31723143
DOI
https://doi.org/10.1038/s41467-019-12970-4
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.
Recommended Citation
Lewandowski J,
Lee J,
Hwang T,
Sunwoo H,
Goldstein J,
Groff A,
Chang N,
Mallard W,
Williams A,
Henao-Meija J,
Flavell R,
Lee J,
Gerhardinger C,
Wagers A,
Rinn J.
The Firre locus produces a trans-acting RNA molecule that functions in hematopoiesis. Nat Commun 2019 Nov 13; 10(1):5137
Comments
This open access article is licensed under a Creative Commons Attribution 4.0 International License