FOXP3 与 hnRNPF 相互作用，调节前体 mRNA 的可变剪接。
FOXP3 interacts with hnRNPF to modulate pre-mRNA alternative splicing.
机构信息
From the Wells Center for Pediatric Research and Department of Pediatrics and.
Benaroya Research Institute at Virginia Mason, Seattle, Washington 98101.
出版信息
J Biol Chem. 2018 Jun 29;293(26):10235-10244. doi: 10.1074/jbc.RA117.001349. Epub 2018 May 17.
Abstract
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 -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.
摘要
FOXP3 主要通过调节靶基因的转录来促进调节性 T 细胞的发育和功能。RNA 可变剪接与广泛的生理和病理生理过程有关。我们在这里报告，FOXP3 通过 FOXP3 的外显子 2 编码区和 hnRNPF 的第二个准 RNA 识别基序（qRRM）与异质核核糖核蛋白（hnRNP）F 相关联。FOXP3 抑制 hnRNPF 与其靶 pre-mRNA 结合的能力，从而调节 RNA 可变剪接。此外，在未分化的调节性 T 细胞（Tregs）中过表达小鼠 hnRNPF 会降低其抑制功能。因此，我们的研究确定了 FOXP3 调节 mRNA 可变剪接以调节调节性 T 细胞功能的新机制。
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