Fox-3 and PSF interact to activate neural cell-specific alternative splicing.
Fox-3 and PSF interact to activate neural cell-specific alternative splicing.
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FOX-3和PSF相互作用以激活神经细胞特异性替代剪接。
DOI：
10.1093/nar/gkq1221
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发表时间：
2011-04
影响因子：
14.9
通讯作者：
Kawamoto S
中科院分区：
文献类型：
--
作者：
Kim KK;Kim YC;Adelstein RS;Kawamoto S
在哺乳动物中，Fox-1家族（Fox -1 family, Fox-1）蛋白由Fox-1 （A2BP1）、Fox-2 （Rbm9）和Fox-3 （NeuN）组成，它们与RNA元件UGCAUG结合并调节mrna前剪接的选择性。然而，狐狸调控剪接的机制在很大程度上是未知的。我们分析了三种Fox蛋白的表达模式以及非肌肉肌球蛋白重链（NMHC） II-B的盒式外显子N30在小鼠中枢神经系统中的神经细胞特异性选择性剪接。荧光活化细胞分选后的组织学和生化分析表明，N30包涵体与Fox-3表达呈正相关。此外，我们通过亲和层析鉴定了聚嘧啶束结合蛋白相关剪接因子（PSF）是与Fox-3相互作用的蛋白。在培养细胞中，Fox-3对N30包合的增强取决于PSF的存在。PSF以依赖ugcag的方式增强N30的包含性，尽管它不直接与该元件结合。Fox-3在内源性NMHC II-B转录物中以psf依赖的方式被募集到N30下游的UGCAUG元件。本研究首次发现PSF是Fox蛋白的共激活因子，并提供证据表明Fox-3和PSF的相互作用是Fox蛋白通过下游内含子增强子调节替代外显子激活的机制的组成部分。
Fox-1 family (Fox) proteins, which consist of Fox-1 (A2BP1), Fox-2 (Rbm9) and Fox-3 (NeuN) in mammals, bind to the RNA element UGCAUG and regulate alternative pre-mRNA splicing. However the mechanisms for Fox-regulated splicing are largely unknown. We analyzed the expression pattern of the three Fox proteins as well as neural cell-specific alternative splicing of a cassette exon N30 of nonmuscle myosin heavy chain (NMHC) II-B in the mouse central nervous system. Histological and biochemical analyses following fluorescence-activated cell sorting demonstrate a positive correlation of N30 inclusion and Fox-3 expression. Further, we identified polypyrimidine tract binding protein-associated splicing factor (PSF) as an interacting protein with Fox-3 by affinity-chromatography. In cultured cells, enhancement of N30 inclusion by Fox-3 depends on the presence of PSF. PSF enhances N30 inclusion in a UGCAUG-dependent manner, although it does not bind directly to this element. Fox-3 is recruited to the UGCAUG element downstream of N30 in the endogenous NMHC II-B transcript in a PSF-dependent manner. This study is the first to identify PSF as a coactivator of Fox proteins and provides evidence that the Fox-3 and PSF interaction is an integral part of the mechanism by which Fox proteins regulate activation of alternative exons via a downstream intronic enhancer.
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影响因子：
14.9
作者：
Goo YH;Cooper TA
通讯作者：
Cooper TA
影响因子：
10.5
作者：
HUH, GS;HYNES, RO
通讯作者：
HYNES, RO
影响因子：
14.9
作者：
Fukumura, Kazuhiro;Kato, Ayako;Inoue, Kunio
通讯作者：
Inoue, Kunio
影响因子：
4.5
作者：
Damianov, Andrey;Black, Douglas L.
通讯作者：
Black, Douglas L.
DOI：
10.1006/bbrc.2001.4617
发表时间：
2001-03-30
影响因子：
3.1
作者：
Lieberman, AP;Friedlich, DL;Fischbeck, KH
通讯作者：
Fischbeck, KH