FLICR, a long noncoding RNA, modulates Foxp3 expression and autoimmunity
FLICR neighbors Foxp3 in mouse and human genomes . FLICR lncRNA is present across mammalian species with clear stretches of sequence conservation and FLICR transcripts in the mouse genome have four different isoforms of varying lengths (566,737, 3,278, and 4,150 bp) that share two exonic elements and an intron, located 1.8 kb upstream of the Foxp3 transcriptional start site (TSS) .
FLICR (Foxp3 long intergenic noncoding RNA) is a negative regulator that regulates key transcription factor FoxP3 expression in Tregs, resulting in twofold- to fivefold-lower levels of FoxP3 protein . Flicr acts only in cis. It does not affect DNA methylation, but modifies chromatin accessibility in the conserved noncoding sequence 3 (CNS3)/Accessible region 5(AR5) region of Foxp3 . As a result, FLICR curtails Treg activity, markedly promotes autoimmune diabetes and, conversely, restrains antiviral responses . Also, this mechanism of FoxP3 control may allow escape from dominant Treg control during infection or cancer, at the cost of heightened autoimmunity .
FLICR is specifically expressed in Tregs .
FLICR is highly conserved across mammalian species .
Labs working on this lncRNA
- Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.
- Zemmour D, Pratama A, Loughhead SM, Mathis D, Benoist C. Flicr, a long noncoding RNA, modulates Foxp3 expression and autoimmunity. Proc Natl Acad Sci U S A. 2017 Apr 25;114(17):E3472-E3480.
>gi|110437700|ref|NR_147988.1|Homo sapiens FOXP3 regulating long intergenic non-coding RNA (FLICR), long non-coding RNA