Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 293, Issue 26, Pages 10235-10244Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.RA117.001349
Keywords
forkhead box P3 (FOXP3); heterogeneous nuclear ribonucleoprotein (hnRNP); RNA splicing; RNA-protein interaction; immunology; Treg; immunosuppression; alternative splicing
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Funding
- National Institutes of Health [R21 AI110773, R01 AI085046]
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FOXP3 promotes the development and function of regulatory T cells mainly through regulating the transcription of target genes. RNA alternative splicing has been implicated in a wide range of physiological and pathophysiological processes. We report here that FOXP3 associates with heterogeneous nuclear ribonucleoprotein (hnRNP) F through the exon 2-encoded region of FOXP3 and the second quasi-RNA recognition motif (qRRM) of hnRNPF. FOXP3 represses the ability of hnRNPF to bind to its target pre-mRNA and thus modulates RNA alternative splicing. Furthermore, overexpression of mouse hnRNPF in in vitro-differentiated regulatory T cells (Tregs) reduced their suppressive function. Thus, our studies identify a novel mechanism by which FOXP3 regulates mRNA alternative splicing to modulate the function of regulatory T cells.
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